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INTRODUCTION: Whether carbon dioxide (CO2) affects systemic oxidative phenomena under conditions of endotoxemia is not sufficiently clarified. The study aimed to assess the impact of moderate acute hypercapnia on the respiratory burst of circulating neutrophils in mechanically ventilated endotoxemic rabbits. MATERIAL AND METHODS: Twenty-four endotoxemic rabbits were mechanically ventilated with standard or CO2-enriched gas mixture in order to obtain isooxic hypercapnia. At a baseline point and following 180 min of hypercapnic ventilation, luminol-dependent chemiluminescence (CL) of circulating neutrophils and serum 2-thiobarbituric acid reactive substance (TBARS) concentrations were measured. Throughout the study, leukocyte and neutrophil counts, pH status, circulatory parameters and body temperature were also assessed. RESULTS: Following 180 min of hypercapnic ventilation, opsonized zymosan (OZ)-stimulated neutrophils showed lower CL vs. the control group (p = 0.004). Other parameters studied were not affected. CONCLUSIONS: Short-term isooxic hypercapnia in endotoxemic rabbits preserves circulating neutrophil count pattern and reactive oxygen species (ROS) generation, but it may reduce phagocytosis.
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The purpose of this work was i) to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model of dexmedetomidine (DEX) in New Zealand White rabbits, ii) to investigate the influence of the age and weight of the animals on the model parameters, and iii) to assess the linearity of DEX PKs in the examined dose range. This was a prospective, crossover study, using a total of 18 New Zealand White rabbits. DEX was administered as a single intravenous bolus injection in the doses from 25 to 300 µg kg-1 . Each New Zealand White rabbit was given the same dose of drug in its three developmental stages. To determine the DEX PK, seven blood samples were taken from each animal. The pedal withdrawal reflex was the PD response used to assess the degree of sedation. Nonlinear mixed effects modelling was used for the population PK/PD analysis. The typical value of elimination clearance was 0.061 L min-1 and was 35% higher in younger New Zealand White rabbits compared with older animals. The PK of DEX was linear in the examined concentration range. Age-related changes in sensitivity to DEX were not detected. The results suggest that due to the pharmacokinetics, younger animals will have lower DEX concentrations and a shorter duration of sedation than older animals given the same doses of DEX per kg of body weight.
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Dexmedetomidina/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Modelos Biológicos , Factores de Edad , Animales , Peso Corporal , Estudios Cruzados , Dexmedetomidina/farmacocinética , Dexmedetomidina/farmacología , Relación Dosis-Respuesta a Droga , Hipnóticos y Sedantes/farmacocinética , Hipnóticos y Sedantes/farmacología , Inyecciones Intravenosas , Dinámicas no Lineales , Estudios Prospectivos , ConejosRESUMEN
Local anesthetics (LAs) are capable of influencing cell viability in systemic immunity and may also modify metabolism of those present in umbilical cord blood (UCB) following obstetric neuraxial analgesia and anaesthesia. Data regarding UCB immature cells, important for the neonate and critical for putative UCB transplantations, are lacking. LAs are capable of stimulating intracellular nitric oxide (NO) in human neutrophils; no information is available concerning newly perpetuated cells and its potential association with viability. The study aimed at assessing the LAs influence on the cell viability and intracellular NO production by UCB CD34+CD133- and CD34+ CD133+ cell populations. Mononuclear cells separated from UCB samples (n = 19) were incubated with bupivacaine (0.0005, 0.005, 1 mM), lidocaine (0.002, 0.02, 4 mM), and ropivacaine (0.0007, 0.007, 1.4 mM) for 4 h. Flow cytometry was applied for the assessment of cell viability and intracellular NO generation in CD34+CD133- and CD34+CD133+ cell populations using annexinV/7-AAD and DAF-2DA stainings, respectively. CD34+CD133+ cells showed less pronounced late apoptosis and necrosis as compared to CD34+CD133-population. Intracellular NO generation was comparable between both cell populations studied. LAs neither influenced cell viability nor changed NO production in either population. LAs do not interfere with viability and intracellular NO generation in the UCB CD34+CD133- and CD34+CD133+ cell populations.
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BACKGROUND: Whether local anesthetics exert anti-inflammatory effects in fetal and newborn systemic neutrophils is unclear. The aim of the present study was to assess the effects of bupivacaine and lidocaine on the respiratory burst of cord blood neutrophils in vitro compared with adult cells. METHODS: Whole cord blood (n = 12) and control adult blood samples (n = 7) were incubated with bupivacaine (0.0005, 0.005, 0.05, 1 mmol/l) and lidocaine (0.002, 0.02, 0.2, 4 mmol/l) for 1 and 4 h. The production of reactive oxygen species (ROS) by unstimulated neutrophils and the phorbol myristate acetate-induced oxidative burst were assessed by flow cytometry. A subset of neutrophils showing high fluorescence intensity (rho+) was analyzed separately. RESULTS: After 1 h incubation, local anesthetics decreased the respiratory burst in whole cord blood and adult neutrophils in a similar manner. At the clinically relevant concentration of 0.0005 mmol/l, bupivacaine was active, but its effect in cord blood cells could not be detected after 4 h. The cord blood rho+ cell subset was unresponsive to the inhibitory action of bupivacaine. In rho+ neutrophils, basal ROS production was stimulated by lidocaine at the lowest concentration tested. CONCLUSION: Bupivacaine and lidocaine can decrease the respiratory burst in neutrophils of term newborns.
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Anestésicos Locales/farmacología , Antiinflamatorios/farmacología , Sangre Fetal , Neutrófilos/efectos de los fármacos , Estallido Respiratorio/efectos de los fármacos , Adulto , Bupivacaína/farmacología , Estudios de Casos y Controles , Relación Dosis-Respuesta a Droga , Femenino , Sangre Fetal/citología , Citometría de Flujo , Humanos , Lidocaína/farmacología , Masculino , Neutrófilos/citología , Especies Reactivas de Oxígeno/metabolismo , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: Systemic inflammation may change the bioavailability and pharmacokinetics of opioids. However, there are insufficient data on morphine pharmacokinetics in mild inflammatory conditions. This study aimed to determine the pharmacokinetics of morphine during low-dose endotoxemia in rabbits. DESIGN: In two experiments (separated by a 14-day washout period), 10 rabbits received intravenous morphine at a dose of 3 mg/kg. In the second set of experiments, morphine infusion was preceded by low-dose endotoxemia induced with lipopolysaccharide (Escherichia coli 0111: B4) at a dose of 5 µg/kg. The kinetics of systemic morphine concentrations and chosen physiological parameters were measured at specific time intervals up to 6 hours after morphine administration. RESULTS: In endotoxemia, decreased elimination half-life (P = 0.017), mean residence time (P = 0.022), and volume of distribution (P = 0.037) as well as an increased elimination rate constant (P = 0.013) and total body clearance (P = 0.023) were noted. The inverse linear correlation between morphine clearance versus the percentage (%) change in body temperature and pulse rate observed under control conditions was abolished under endotoxemia. CONCLUSIONS: Low-dose endotoxemia is correlated with significant alterations in morphine pharmacokinetics in rabbits, leading to the faster elimination of the drug. CLINICAL IMPLICATIONS: These findings may have important implications in patients with low-grade inflammation and imply the need to modify morphine dosing regimens to ensure optimal analgesia. The issue warrants further experimental and clinical investigation.
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Analgésicos Opioides/farmacología , Endotoxemia/metabolismo , Morfina/farmacocinética , Animales , Modelos Animales de Enfermedad , Endotoxemia/inducido químicamente , Escherichia coli , Femenino , Semivida , Lipopolisacáridos/toxicidad , Masculino , ConejosRESUMEN
There are immunological consequences to the method by which neutrophils undergo cell death. Neutrophil apoptosis, called silent death, leads to the resolution of inflammation, while NETosis deepens and prolongs the inflammatory response and is associated with a worse prognosis of severe infections, e.g., sepsis. Besides nociceptive inhibition, local anaesthetics modulate leukocyte functions, even at low, clinically relevant concentrations. There is currently no data on ropivacaine NETosis, and this study aimed to evaluate the impact of clinical concentrations of ropivacaine (0.0007, 0.007 and 1.4 mmol/L) and lidocaine (0.002, 0.02 and 4 mmol/L) on apoptosis and NETosis of adult peripheral blood neutrophils after 2 h of incubation. Neutrophil identification, apoptosis and NETosis were evaluated by flow cytometry using forward and side scatter characteristics and fluorescent labelling: CD15 for neutrophils identification; Annexin V and propidium iodide for apoptosis and citrullinated histone H3 and myeloperoxidase for NETosis. Lidocaine (4 mmol/L) and ropivacaine (1.4 mmol/L) induced early apoptosis in resting but not in stimulated neutrophils. Low doses of ropivacaine (0.0007 and 0.007 mmol/L) decreased the number of late apoptotic neutrophils, and the lowest dose slightly increased their viability. None of the drugs induced NETosis in resting neutrophils but decreased NETosis at clinical concentrations compared to PMA-stimulated 4 mM lidocaine, PMA-stimulated control, and 1.4 mM ropivacaine. The effect of lidocaine and ropivacaine on apoptosis and NETosis depended on neutrophil stimulation and drug concentrations. Ropivacaine tends to be cytoprotective at concentrations observed in plasma under local anaesthesia. Lidocaine enhanced NETosis at high concentration only in stimulated neutrophils. Thus, both drugs have the ability to change the course of inflammation.
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We investigated how potato exposed to a chemical agent could activate nitric oxide (NO)-dependent events facilitating more potent defense responses to a subsequent pathogen attack. Obtained data revealed that all applied inducers, i.e., ß-aminobutyric acid (BABA), γ-aminobutyric acid (GABA), laminarin, or 2,6-dichloroisonicotinic acid (INA), were active stimuli in potentiating NO synthesis in the primed potato. It is assumed, for the mechanism proposed in this paper, that priming involves reversible S-nitrosylated protein (S-nitrosothiols [SNO]) storage as one of the short-term stress imprint components, apart from epigenetic changes sensitized by NO. Based on BABA- and GABA-induced events, it should be stated that a rise in NO generation and coding the NO message in SNO storage at a relatively low threshold together with histone H2B upregulation might create short-term imprint activation, facilitating acquisition of a competence to react faster after challenge inoculation. Laminarin elicited strong NO upregulation with an enhanced SNO pool-altered biochemical imprint in the form of less effective local recall, nevertheless being fully protective in distal responses against P. infestans. In turn, INA showed the most intensified NO generation and abundant formation of SNO, both after the inducer treatment and challenge inoculation abolishing potato resistance against the pathogen. Our results indicate, for the first time, that a precise control of synthesized NO in cooperation with reversible SNO storage and epigenetic modifications might play an important role in integrating and coordinating defense potato responses in the priming phenomenon.
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Óxido Nítrico/metabolismo , Solanum tuberosum/efectos de los fármacos , Solanum tuberosum/metabolismo , Aminobutiratos/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Glucanos , Ácidos Isonicotínicos/farmacología , Polisacáridos/farmacología , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
OBJECTIVES: Systemic ß-endorphin, an endogenous opioid and stress hormone, has been demonstrated to correlate with the postoperative pain intensity, however its putative role as a postoperative pain biomarker has not been cleared. METHODS: Thirty patients scheduled for elective hysterectomy were included into the study. Postoperative pain was assessed by a numeric rating scale from 0 to 10. Plasma morphine concentrations were determined using high performance liquid chromatography with UV detection. Plasma ß-endorphin concentrations were measured by a radioimmunoassay. RESULTS: Administration of morphine in intravenous infusion turned out to be a markedly better method of morphine administration up to 4th hour postoperatively regarding both drug concentration and pain rating. A significant correlation between systemic ß-endorphin concentration and pain rating at the 4th postoperative hour was found. No association between morphine and ß-endorphin concentrations was detected. CONCLUSION: Systemic ß-endorphin is not an appropriate pain marker in postoperative gynaecologic patients.
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Histerectomía , Morfina/administración & dosificación , Morfina/sangre , Dolor Postoperatorio/tratamiento farmacológico , betaendorfina/sangre , Abdomen/cirugía , Adulto , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/sangre , Biomarcadores/sangre , Monitoreo de Drogas/métodos , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Histerectomía/métodos , Infusiones Subcutáneas/métodos , Persona de Mediana Edad , Dolor Postoperatorio/sangre , Resultado del TratamientoRESUMEN
OBJECTIVE: Local anesthetics are able to inhibit inflammatory phenomena. The influence of bupivacaine broadly applied in obstetrical anesthesia on the reactive oxygen species (ROS) production is a matter of controversy. The study was aimed at elucidation of the influence of racemic bupivacaine on the opsonized zymosan (OZ) stimulated-peripheral blood chemiluminescence (CL) in laboring women, reflecting the reactive oxygen species (ROS) production associated with phagocytosis. MATERIAL AND METHODS: Blood samples drawn from 8 healthy parturients in active spontaneous labor and from 5 healthy non-pregnant controls were incubated with the 0.3, 30, and 3000 microM bupivacaine concentrations and then luminol-dependent OZ-stimulated whole blood CL was assessed. RESULTS: Bupivacaine depressed CL; however the inhibitory effect was significant only at the highest, clinically irrelevant concentration (3000 microM), in parturients being comparable to that observed in non-pregnant women. CONCLUSIONS: Bupivacaine at clinically relevant concentrations does not influence ROS production accompanying phagocytosis in peripheral blood of laboring women. The effect is comparable in parturients and non-pregnant controls.
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Anestésicos Locales/farmacología , Bupivacaína/farmacología , Luminiscencia , Complicaciones del Trabajo de Parto/tratamiento farmacológico , Especies Reactivas de Oxígeno/sangre , Adulto , Anestesia Obstétrica/métodos , Femenino , Humanos , Mediciones Luminiscentes/métodos , Complicaciones del Trabajo de Parto/sangre , Embarazo , Valores de Referencia , Adulto JovenRESUMEN
It is estimated that about 1/4 of mothers-to-be misuse psychoactive substances, and smoking cigarettes is most prevalent. Medical problems of addicted pregnant women involve direct toxicological influences or abstain effects of substances misused, but are also due to consequences of their chronic use, superimposed by infection, poor nutrition and psychiatric problems. Psychoactive substances have also a negative impact on pregnancy, the fetus, and the neonate. Tobacco addiction may accompany other dependencies and be one of useful markers of them. Smoking cigarettes in the substance dependent pregnant women also substantially increases the risk of both maternal and fetal complications. Special hazards are connected with labor and surgical interventions. There is a strong need to multidisciplinary approach to dependencies in pregnancy. Pregnancy should be considered an opportune time for their detection and treatment.
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Enfermedades del Recién Nacido/epidemiología , Trastornos Mentales/epidemiología , Complicaciones del Embarazo/epidemiología , Fumar/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Causalidad , Comorbilidad , Femenino , Humanos , Recién Nacido , Trastornos Mentales/diagnóstico , Trastornos Mentales/terapia , Polonia/epidemiología , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/terapia , Prevención del Hábito de Fumar , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/terapiaRESUMEN
A global increase in addictions also affects pregnant women. In mothers-to be most frequent is tobacco dependence, despite broad spread of information on negative influence of smoking on the mother and infant. Other substance misuse as ethanol but also illicit drugs may additionally coexist in pregnancy. Smoking cigarettes underlies complications of pregnancy and parturition and babies of smoking mothers present with lower birthweight. As a disorder involving a number of pathologies tobacco dependence in pregnant women and parturients implicates an increased peripoerative risk, especially for respiratory and cardiac complications. Anesthetic management of choice is neuraxial blockades, both for labor analgesia and surgery. On contact with tobacco dependent pregnant and parturient patient an anesthetist should also take an advantage for smoking cessation consulting.
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Parto Obstétrico/métodos , Complicaciones del Embarazo/epidemiología , Efectos Tardíos de la Exposición Prenatal , Contaminación por Humo de Tabaco/estadística & datos numéricos , Tabaquismo/epidemiología , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Alcoholismo/epidemiología , Analgesia Obstétrica/métodos , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Parto/efectos de los fármacos , Embarazo , Complicaciones del Embarazo/prevención & control , Cese del Hábito de Fumar/métodos , Contaminación por Humo de Tabaco/prevención & control , Tabaquismo/prevención & controlRESUMEN
Nitric oxide (NO) generation by systemic neonatal neutrophils is not clarified. It is also not known whether local anaesthetics (LAs) transferred to the fetal systemic circulation following maternal epidural blockade may affect this process. In the present study, NO generation was evaluated in neutrophils from cord blood (CB, n = 11) and adult blood (n = 10) following exposure to bupivacaine (0.0005, 0.005, 1 mM), lidocaine (0.002, 0.02, 4 mM) and ropivacaine (0.0007, 0.007, 1.4 mM) using flow cytometry, as well as indirectly by determining nitrite concentrations in cell incubation media. To determine the role of NO synthase (NOS) isoforms in NO generation following exposure to LAs, experiments were repeated in the presence of the NOS inhibitors, NG-nitro-L-arginine methyl ester and aminoguanidine; in addition, the expression of NOS isoforms was analysed. CB neutrophils produced less NO than adult neutrophils. LAs, especially ropivacaine and lidocaine, stimulated neutrophil NO generation, but in CB neutrophils this effect was negligible at clinically relevant drug concentrations. A mechanism involving NOS activity was responsible for the observed phenomena. In conclusion, LAs are able to upregulate neutrophil NO production, but in neonates this effect is likely to be clinically insignificant.
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Anestésicos Locales/efectos adversos , Células Sanguíneas/efectos de los fármacos , Células Sanguíneas/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Óxido Nítrico/metabolismo , Adulto , Bupivacaína/efectos adversos , Femenino , Citometría de Flujo , Humanos , Lidocaína/efectos adversos , Masculino , Óxido Nítrico Sintasa/análisis , Ropivacaína/efectos adversos , Adulto JovenRESUMEN
Smoking cessation in the perioperative period allows a substantial reduction of a number of anesthetic and surgical complications. They primarily include pathology and adverse reactions of respiratory, cardiovascular and nervous systems and also alterations in wound and bone healing. There is no doubt that long-term (several months) tobacco abstinence reduces the complication risk; however, the significance of short-term smoking cessation is being discussed. Additionally, due to increased patient motivation surgical operation poses a "teachable moment" to be captured for quitting permanently. Interventions for preoperative smoking cessation effectively change smoking behavior and should be widely offered to surgical patients. Oral recommendations should possibly be supported by pharmacotherapy. Nicotine replacement therapy and bupropion proved to be effective and safe in the perioperative period.
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Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios , Cese del Hábito de Fumar/métodos , Anestesia/métodos , Humanos , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
Pathological fear of childbirth known as "tokophobia" affects about 6-10% pregnancies and is of concern mainly because of remarkable sequele regarding women's morbidity, the neurobehavioral development of their children, and cesarean section on maternal request (CSMR). Fear of labor is a multidimensional problem involving a number of biological, psychological and social background factors and may be divided into primary and secondary tokophobia and tokophobia as a symptom of depression. Fear of childbirth is closely related to the fear of labor pain. It appears that women who experience fear, suffer from more pain due to alterations in the mechanisms of pregnancy induced analgesia. Despite no relevant connection between tokophobia and request for effective analgesia for labor pain relief, neuraxial techniques should always be available, especially to women with increased levels of negative emotions. However, epidural analgesia itself may increase fear level at the end and after labor and delivery. The mainstay of tokphobia treatment constitutes psychotherapeutic methods, which decrease negative labor experience; their impact on CSMR is controversial. There is a strong need for multidisciplinary approach to tokophobia due to its complexity and obstetric, anesthesiological, psychological and psychiatric implications.
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Parto Obstétrico/psicología , Miedo , Trabajo de Parto/psicología , Conducta Materna/psicología , Complicaciones del Trabajo de Parto/psicología , Adulto , Ansiedad , Femenino , Humanos , Bienestar Materno , Trastornos Fóbicos/psicología , Embarazo , Autoimagen , Apoyo SocialRESUMEN
OBJECTIVES: Neuraxial methods provide the most effective labor pain relief. This study aimed at assessing anxiety level in parturients requesting epidural analgesia (EA). MATERIAL AND METHODS: Forty five women in spontaneous, active labor were enrolled, both primiparas (n=36) and multiparas (n=9). Anxiety was assessed by means of Spielberger State and Trait Anxiety Inventory (STAI) before administration of EA, and pain was measured by visual-analog scale (VAS) before and after analgesia. RESULTS: In all the studied parturients state anxiety was strikingly higher than the trait (53.9 +/- 11.8 vs. 39.3 +/- 8.4; P < 0.0001); the difference appeared insignificant in multiparas only. State anxiety was comparable independently of parity, labor outcome and systemic opioid administration. No association between anxiety level and labor pain intensity preceding analgesia, the duration of labor stages and demographic parameters could be found. However, a negative correlation between state anxiety and pain intensity reported after EA administration was noted (R = -0.315, p = 0.040), and, in cases of physiological labor, a negative association between state anxiety and the neonate Apgar score at the 1st minute after birth could be observed (R = -0.337, p = 0.047, Spearman rank test). CONCLUSIONS: In parturients requesting EA, state anxiety level is increased and not connected with the trait. Furthermore, in these women, anxiety appears not to be associated with labor pain but may influence the analgesic effect of the blockade. Anxiety does not determine labor duration and outcome; however, it may be connected with the well-being of the neonate immediately after birth.
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Analgesia Obstétrica , Ansiedad/diagnóstico , Dolor de Parto/tratamiento farmacológico , Dolor de Parto/psicología , Trabajo de Parto/psicología , Analgesia Epidural , Analgésicos Opioides/administración & dosificación , Ansiedad/complicaciones , Femenino , Humanos , Dolor de Parto/complicaciones , Dimensión del Dolor , Paridad , Dolor Pélvico/tratamiento farmacológico , Dolor Pélvico/psicología , EmbarazoRESUMEN
Smoking cigarettes poses a number of relevant medical and social problems. Impact of smoking on pain threshold and tolerance may be of significance for surgical patients, who are prompted to abstain from cigarettes before operation. Association between smoking and pain perception is complex. Experimental data bring evidence for analgesic action of nicotine and tobacco smoke acting via nicotinic acetylochline receptors (nAChR). However, clinical studies are unequivocal. Smoking is connected with some pain syndromes. Smokers take much more analgesics than non-smokers and probability of developing opioid dependence is increased in this group of patients. Smokers also present with altered mechanism of stress-induced analgesia and both gender and pain modalities influence their pain perception. Some studies demonstrate increased requirements for postoperative opioid analgesia in smoking patients. Strategies for postoperative pain treatment in smokers should involve regional techniques and clonidine.
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Nicotina/farmacología , Umbral del Dolor/efectos de los fármacos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/fisiopatología , Fumar/efectos adversos , Analgésicos Opioides/uso terapéutico , Humanos , Dimensión del Dolor , Dolor Postoperatorio/etiología , Periodo PosoperatorioRESUMEN
N,N-Dialanyl protoporphyrin (PP(Ala)2) and diarginine diprotoporphyrinate (PP(Arg)2) are porphyrin photosensitizers that are currently being used in the photodynamic therapy (PDT) of cancer. In the present study, the effects of these agents on the neutrophil respiratory burst in vitro were investigated. In the case of non-stimulated neutrophils, the respiratory burst was significantly increased in the presence of PP(Ala)2 in concentration 5.0mg/l, while in the presence of PP(Arg)2 in the same concentration it did not change. By contrast, both photosensitizers decreased a respiratory burst by neutrophils stimulated with opsonized zymosan. Pre-irradiation of solutions of PP(Ala)2 and PP(Arg)2 with ultraviolet A did not alter the observed responses. The prooxidative effect of PP(Ala)2 is probably due to the stimulation of protein kinase C, which plays a key role in the respiratory burst of non-stimulated cells, whereas the antioxidant effect of both photosensitizers may be explained by their inhibitory effect on EGFR tyrosine kinase, which plays an important role in the respiratory burst of cells stimulated by opsonized zymosan. The lack of effect of the two dyes after UV-A pre-irradiation may be due to rapid self-quenching of UV-A-excited dye molecules to the ground state. The results of this study provide a starting point for experiments in animal models aimed at determining the clinical importance of the observed effects in cancer diagnosis and therapy.
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BACKGROUND: Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) plays a crucial role in vascular function and homeostasis. eNOS activity maintains normal vascular tone, regulates leukocyte-endothelial cell interactions, inhibits platelet aggregation, limits smooth muscle cell proliferation and influences cardiac myocyte contractility. The loss of endothelium-derived NO has been shown to result in serious cardiovascular abnormalities, which may indicate eNOS involvement in the origin/development of cardiovascular disorders. AIM: Evaluation of eNOS mRNA level in the endothelium of human coronary arteries upon opioids treatment (mediators of ischaemic preconditioning) and after incubation with proinflammatory cytokines (stress stimuli). METHODS: Different concentrations of beta-endorphin, endomorphin-1 and endomorphin-2 (alone or in combination with the opioid receptor blocker naloxone) as well as different concentrations of cytokines alone (IL-1beta, TNF-alpha) or in combination were applied to in vitro cultured human coronary artery endothelial cells (HCAEC). After 24 hrs incubation, the cells were harvested, mRNA extracted and relative quantification of eNOS mRNA was conducted using real-time PCR. RESULTS: Opioid treatment altered eNOS expression; however, none of the changes reached a statistically significant level. As for proinflammatory cytokines, both TNF-alpha and IL-1beta substantially down-regulated the eNOS mRNA level (p <0.05). When applied in combination, these cytokines lowered eNOS mRNA even further (p <0.05). The effect was independent of the cytokine combination used. CONCLUSIONS: It was demonstrated that proinflammatory cytokines exert a substantial and statistically significant negative effect on eNOS mRNA level in human coronary artery endothelial cells in in vitro culture. Unfortunately, we were unable to demonstrate significant changes within the eNOS mRNA pool upon opioid treatment. These results indicate that opioids (basal release) do not affect eNOS expression in normal in vitro culture conditions but might do so upon stress stimuli.
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Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/enzimología , Vasos Coronarios/enzimología , Células Endoteliales/enzimología , Interleucina-1/uso terapéutico , Naloxona/uso terapéutico , Narcóticos/uso terapéutico , Óxido Nítrico Sintasa/metabolismo , Factor de Necrosis Tumoral alfa/uso terapéutico , Enfermedades Cardiovasculares/fisiopatología , Humanos , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismoRESUMEN
Cardiovascular risk is increased in cigarette smokers in the perioperative period and smoking cessation results in its decrease. The pilot study has been designed to assess an association between smoking and arterial blood pressure and heart rate during induction of anaesthesia in gynecologic patients. Significance of smoking cessation before operation in this respect should be also assessed. Systolic, diastolic and mean arterial blood pressures and heart rate were assessed before and after the induction of anaesthesia in gynecologic patients subjected to hysterectomy: 27 smokers and 27 non-smokers. Anxiety level and intraoperative fentanyl use were also analyzed. Examined parameters were compared between smokers who were abstinent for at least one day before operation and those who continued smoking. Arterial blood pressure and heart rate were comparable in both smokers and non-smokers and also in both groups before and after the induction of aneasthesia. Smoking did not result in any modulation of anxiety level and intraoperative fentanyl dosage. Smoking cessation was connected with lower mean arterial pressure before the induction (P = 0,037). Cigarette smoking does not modify values of basic haemodynamic parameters during induction of anaesthesia in gynecologic patients. Smoking abstinence for at least one day before surgery may be connected with a lower mean arterial blood pressure before the induction.
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Anestesia Obstétrica , Presión Sanguínea , Frecuencia Cardíaca , Cese del Hábito de Fumar , Fumar/fisiopatología , Adyuvantes Anestésicos/administración & dosificación , Adulto , Ansiedad/etiología , Ansiedad/prevención & control , Monitoreo Ambulatorio de la Presión Arterial , Electrocardiografía Ambulatoria , Femenino , Fentanilo/administración & dosificación , Humanos , Histerectomía/efectos adversos , Periodo Intraoperatorio , Persona de Mediana Edad , Proyectos Piloto , SístoleRESUMEN
Smoking cigarettes adds to risk of anesthesia and surgery, and also may influence anxiety. However, cigarette abstinence may increase preoperative stress. The study aimed at exploring the relationship between smoking and anxiety in gynaecologic patients in the perioperative period, and also finding out whether the abstinence and history of unsuccessful cessation attempts are connected with an anxiety pattern at that time. A relationship between anxiety and postoperative pain should be also examined. In 24 smokers and 24 non-smokers subjected to hysterectomy the anxiety level was examined by means of both Spielberger's state and trait inventory (STAI) and visual-analog scale (VAS) before and following surgery; maximal pain on the first postoperative day was also assessed by VAS scale. Smokers additionally completed an inventory of smoking behavior. Pre- and postoperatively the anxiety level was comparable in both groups. Before surgery but not after it, state anxiety overtopped the trait in both smokers and non-smokers. Postoperatively state anxiety was connected with the trait and morphine consumption. Cigarette abstinence before surgery did not influence anxiety; however, state anxiety correlated with the length of abstinence. In smokers with the history of smoking cessation attempts, preoperative state anxiety was higher. Between smokers and non-smokers no differences in postoperative pain and no significant relationship with the anxiety could be found, Conclusions: 1) Perioperative anxiety is comparable in both smoking and non-smoking gynaecologic patients. 2) Cigarette abstinence before surgery is not connected with any significant anxiety differences. Smokers with the history of unsuccessful cessation attempts preoperatively present with higher state anxiety.