RESUMEN
Cytokines regulate numerous physiological and pathological processes in the central nervous system (CNS), i.e. they function both as immune regulators and neuromodulators. Acting upon the CNS via different ways, cytokines, mainly proinflammatory ones IL-1beta and TNF-alpha, can disturb physiological functions of the CNS, cause neurotoxic and neurodegenerative damage and stimulate IL-1beta synthesis in hypothalamus nuclei and posterior pituitary. They can produce stress-like effects upon the CNS and affect the activity of the axis hypothalamus--pituitary--adrenal glands, levels of neuropeptides in hypothalamic regions of brain, synthesis and utilization of central monoamines. These influences can implement the effects of sensitization, which enhances neuroendocrine responses to later stresses. Microglia and astrocytes, secondary messengers and interaction between hypothalamus and anterior pituitary play an important role in range of these processes as well as in the maintenance of Th1/Th2 cytokine balance.
Asunto(s)
Encéfalo/inmunología , Citocinas/fisiología , Factores Inmunológicos/fisiología , Neuroinmunomodulación , Sistemas de Mensajero Secundario/inmunología , Animales , HumanosRESUMEN
The pattern of incorporation of [14C]uridine showed that in MOLT-3 cells an increased proportion of CTP was synthesized via CTP synthetase, compared to proliferating normal human T lymphocytes at a physiological concentration of cytidine (< 0.5 microM). Furthermore, in the proliferating normal human T lymphocytes similar patterns of incorporation of [14C]uridine were observed in the presence of the physiological concentration of cytidine and after addition of 2 microM of cytidine. In contrast, in the MOLT-3 cells after addition of 2 microM of cytidine the proportion of CTP synthesized by conversion of UTP into CTP was substantially decreased, whereas the salvage of cytidine was proportionally increased. We conclude that the reutilization of uridine is a preferred route in the synthesis of CTP for MOLT-3 cells at physiological concentrations of uridine and cytidine, whereas in proliferating normal human T lymphocytes CTP is largely synthesized through reutilization of cytidine. This difference in salvage of pyrimidine ribonucleosides may be exploited for selective chemotherapy.
Asunto(s)
Ligasas de Carbono-Nitrógeno , Citidina Trifosfato/biosíntesis , Ligasas/metabolismo , Linfocitos T/enzimología , Uridina Quinasa/metabolismo , Radioisótopos de Carbono , Línea Celular , Humanos , Modelos Biológicos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Células Tumorales Cultivadas , Uridina/metabolismoRESUMEN
The role of cytidine triphosphate (CTP) synthetase (EC 6.3.4.2.) in the pyrimidine ribonucleotide metabolism of MOLT-3 human T-ALL cell line cells and normal human T lymphocytes during the cell cycle traverse was studied. Highly pure G1-phase samples and samples enriched in S-phase cells were obtained by counterflow centrifugation. The activity of CTP synthetase in situ, measured in pulse-chase experiments, was similar in the G1-phase and S-phase MOLT-3 cells. In contrast, in S-phase T lymphocytes, an increased activity of CTP synthetase was observed compared with G1-phase T lymphocytes. Nevertheless, the MOLT-3 samples showed an increased activity of CTP synthetase in comparison with either G1-phase or S-phase enriched samples of normal T lymphocytes. Therefore, the increased activity of CTP synthetase of MOLT-3 cells is a cell cycle-independent feature, whereas among normal T lymphocytes, the increase in activity of CTP synthetase that arises after a growth stimulus is more prominent in the S-phase.
Asunto(s)
Ligasas de Carbono-Nitrógeno , Leucemia-Linfoma de Células T del Adulto/enzimología , Ligasas/metabolismo , Linfocitos T/enzimología , Ciclo Celular , Citidina Trifosfato/biosíntesis , Humanos , Nucleótidos/metabolismo , Células Tumorales Cultivadas/enzimología , Uridina/metabolismoRESUMEN
Mycophenolic acid, an inhibitor of the enzyme IMP dehydrogenase, antagonizes the CTP synthetase inhibitor 3-deazauridine in its anti-proliferative effects on MOLT-3 human T leukemia cells. No depletion of CTP occurred, and decreased amounts of 3-deazuridine-triphosphate were measured in cells incubated with mycophenolic acid and 3-deazuridine. Most probably, these phenomena are related to the increased amounts of PRPP observed, which can result in an increased pyrimidine biosynthesis de novo and, as a consequence, a decreased metabolism of 3-deazauridine via the salvage pathway.
Asunto(s)
3-Desazauridina/farmacología , Ligasas de Carbono-Nitrógeno , Inhibidores Enzimáticos/farmacología , IMP Deshidrogenasa/antagonistas & inhibidores , Ligasas/antagonistas & inhibidores , Ácido Micofenólico/farmacología , Fosforribosil Pirofosfato/metabolismo , 3-Desazauridina/antagonistas & inhibidores , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Leucemia , Ribonucleótidos/biosíntesis , Células Tumorales CultivadasRESUMEN
A novel assay of CTP synthetase was developed which allows the processing of large numbers of samples. The amount of glutamate produced by CTP synthetase was determined with glutamate dehydrogenase and the NAD analogue acetyl-pyridine-adenine dinucleotide was used to shift the initial unfavourable equilibrium towards the formation of a-ketoglutarate. The amount of glutamate determined with the assay was comparable to that of CTP. The assay proved to be linear with time up to 90 min and protein concentrations up to 520 micrograms/ml. However, at low protein concentrations as well as at early time points a lag phase was observed. This hysteretic phenomenon of CTP synthetase may be due to the association-dissociation equilibrium that exists between the various polymerisation states of the enzyme.
Asunto(s)
Ligasas de Carbono-Nitrógeno , Ligasas/análisis , Ligasas/metabolismo , Hígado/enzimología , Animales , Bovinos , Coenzimas , Glutamato Deshidrogenasa , Glutamatos/análisis , Glutamatos/metabolismo , Ácido Glutámico , Indicadores y Reactivos , Cinética , Ligasas/aislamiento & purificación , NAD/análogos & derivados , Unión Proteica , Espectrofotometría Ultravioleta/métodosRESUMEN
Elutriation of human lymphoblastic cells has to be performed at a flow rate of 13 ml/min at a temperature of 10 degrees C to retain a high cell viability. Cell cycle analysis of elutriated cells on the basis of their DNA contents is inaccurate. The combined detection of BrdUrd incorporated into the DNA and analysis of the DNA content offers an alternative. After elutriation, fractions of cells with increased percentages of either G1 or S phase cells can be selected on the basis of the median cell size as established by a coulter counter channelyzer.
Asunto(s)
Linfocitos T/citología , Ciclo Celular/fisiología , División Celular/fisiología , Fraccionamiento Celular/métodos , Separación Celular/métodos , Células Cultivadas , Centrifugación , ADN/análisis , HumanosRESUMEN
A new method is described for determining the activity of a monooxygenase, acting by specific hydroxylation at the 2- position of the aromatic ring of estrogenic compounds with the formation of catechol estrogens. The procedure is based on separation of the catechol estrogen product from the substrate by high performance reversed-phase chromatography with amperometric detection in a thin-layer flow-cell by electrooxidation at a graphite-paste anode. Due to the very high detector sensitivity for the enzymatically generated product and an uncomplicated overall performance, the method offers great advantages over the radioenzymatic assay described earlier.
Asunto(s)
Citocromo P-450 CYP1A1 , Microsomas Hepáticos/enzimología , Esteroide Hidroxilasas/análisis , Animales , Cromatografía Líquida de Alta Presión , Electroquímica , Estriol , Estrógenos/análisis , Cinética , Métodos , RatasRESUMEN
Incorporation of 14C-uridine into UTP and CTP and fluxes of label through these nucleotide pools to RNA and DNA were greater in MOLT-3 cells compared to T-lymphocytes. In growth-arrested, differentiated MOLT-3 cells overall incorporation of radiolabel into nucleotides and nucleic acids was lowered compared to exponentially growing cells. Turnover of UTP and CTP however, retained the profile of exponentially growing MOLT-3 cells, implicating the characteristically higher conversion of UTP to CTP is independent of the MOLT-3 cells proliferative capacities. We conclude that drugs interfering with CTP-synthetase activity are good candidates to be used as selective substances in the battle against T-ALL.
Asunto(s)
Linfocitos T/metabolismo , Uridina/metabolismo , Radioisótopos de Carbono , Diferenciación Celular/efectos de los fármacos , División Celular , Línea Celular , Citidina Trifosfato/metabolismo , Humanos , Técnicas In Vitro , Cinética , Ácidos Nucleicos/biosíntesis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Técnica de Dilución de Radioisótopos , Linfocitos T/citología , Acetato de Tetradecanoilforbol/farmacología , Uridina Trifosfato/metabolismoRESUMEN
The development of sophisticated medical services in the Middle East has resulted in the need for training programmes for staff in all disciplines of health care. Operating Department Assistants (ODAs/Anesthetic Technicians) are essential operating theatre personnel, forming an integral part of the operating theatre team. This paper is designed as a teaching guide for Anesthetic Technicians in training. It lists in point form the essential services that should be provided in each of the seven identifiably different work periods in the Anesthetic Technician's working day.
Asunto(s)
Técnicos Medios en Salud/educación , Anestesiología , Anestesiología/educación , Competencia Clínica , Humanos , Arabia Saudita , Recursos HumanosRESUMEN
Esmolol attenuates hemodynamic responses to tracheal intubation and extubation in young patients, but has less well documented pharmacokinetics and efficacy in older patients. Following cataract surgery, application of pressure on the eye during eye bandaging may have vasomotor effects. The present study of older patients having cataract surgery investigated 1) the effects of normal saline 1.0 ml. 10kg(-1) or esmolol 4.0 mg.kg(-1) IV given 90 secs prior to tracheal intubation and of normal saline 0.5 ml.10 kg(-1) or esmolol 2.0 mg.kg(-1) IV given 60 sec prior to each of eye bandaging and tracheal extubation; 2) the time to onset and duration of action of esmolol; 3) the cardiovascular effects of eye bandaging. Esmolol attenuated the cardiovascular effects of tracheal intubation, eye bandaging and tracheal extubation, but caused relative bradycardia and hypotension after induction and hypotension after extubation. Its effect occurred within 60-90 secs and lasted about 6 mins. Pressure on the eye during bandaging in those not given esmolol caused hypertension without tachycardia.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Extracción de Catarata , Hemodinámica/efectos de los fármacos , Propanolaminas/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Intubación Intratraqueal , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
A prospective study was undertaken on 169 healthy young patients undergoing elective ear, nose and throat surgery to assess the intraoperative effects on heart rate, blood pressure and bronchomotor tone of MAC in nitrous oxide concentrations of halothane (0.4 to 0.6%), isoflurane (0.6 to 0.8%) and enflurane (0.8 to 1%). All the agents produced a progressive slowing of the heart rate during anesthesia. Halothane did so most profoundly, resulting in a maximum slowing of 40 beats-1 compared with a maximum slowing of about 20 beats min-1 with both isoflurane and enflurane. The three volatile agents also produced progressively similar degrees of hypotension during anesthesia. The hypotension produced by enflurane occurred earliest and was most profound; that produced by isoflurane occurred less early and was less severe, but occurred earlier and was more severe than that produced by halothane. Neither halothane, isoflurane nor enflurane appeared to have any effect on bronchomotor tone.
Asunto(s)
Anestesia por Inhalación , Presión Sanguínea/efectos de los fármacos , Bronquios/efectos de los fármacos , Enflurano , Halotano , Frecuencia Cardíaca/efectos de los fármacos , Isoflurano , Procedimientos Quirúrgicos Operativos , Adolescente , Adulto , Presión Sanguínea/fisiología , Bronquios/fisiología , Niño , Preescolar , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Psychiatric patients receiving phenothiazine, tricyclic antidepressant and antiparkinsonian drugs for prolonged periods, occasionally develop mydriasis and angle closure glaucoma. Suxamethonium, usually given to modify the convulsion of electroconvulsive therapy (ECT) increases intraocular pressure (IOP) by about 7-8 mmHg, the increase being maximal and having returned to baseline 2 min and 6 mins after injection, respectively. We studied the effects on IOP of an electrically induced convulsion following induction of anesthesia using methohexitone 1 mg.kg(-1) and suxamethonium 0.5 mg.kg(-1) in 21 consecutive cooperative psychiatric patients, all receiving antipsychotropic drugs. IOP was recorded sequentially from before induction of anesthesia to after resumption of spontaneous respiration. Their mean IOP was 15.3 (SD 3.7) mmHg prior to induction of anesthesia, 13.5 (SD 3.5) mmHg after loss of eyelash reflex following injection of methohexitone, 16.1 (SD 2.4) mmHg after cessation of muscle fasciculations induced by suxamethonium, 19.2 (SD 5.6) mmHg after cessation of convulsion and 15.5 (SD 4.4) mmHg following resumption of regular spontaneous respiration. The successive stepwise changes in the mean IOP were all statistically significant (p < 0.001 each change compared with the preceding pressure; paired 't' tests). These data reveal that the reduction in IOP produced by methohexitone is reversed by the increase in IOP produced by suxamethonium. Collated with the time course of the effects of barbiturates and suxamethomium on IOP, the increase in IOP observed following the induced convulsion was not greater than that expected after suxamethonium alone, suggesting that the induced convulsion during ECT does not pose an ocular hazard to psychiatric patients receiving medications which have iatrogenic glaucomatous potential.
Asunto(s)
Terapia Electroconvulsiva , Presión Intraocular , Adulto , Anciano , Femenino , Humanos , Masculino , Metohexital/farmacología , Persona de Mediana Edad , Método Simple Ciego , Succinilcolina/farmacologíaRESUMEN
The stress response to tracheal intubation may be obtunded by opioids given with induction of anesthesia. Tramadol is an opioid acting on mu-receptors and the monoaminergic pain modulating systems. This study examined vasomotor responses to tracheal intubation after equipotent doses of tramadol, nalbuphine and pethidine (3.0, 0.3 mg/kg(-1), and 1.5 mg/kg(-1), respectively), and placebo, given prior to induction of anesthesia in 118 healthy patients. Premedication and induction of anesthesia were standardized. Recordings of HR and SAP were made prior and subsequent to induction of anesthesia, and at 1, 3, 5 and 7 minutes after tracheal intubation. Prior to laryngoscopy and intubation, HR increased in all groups (p < or = 01, all comparisons), but least so after nalbuphine, whilst SAP remained unchanged after placebo, tramadol and pethidine, but fell after nalbuphine (p < 0.025). Maximum increases in HR (p < or = 0.005, all comparisons) and SAP (p < or = 0.02, all comparisons) occurred one minute after intubation. Maximum HR after placebo (108 SD 15 bpm), tramadol (107 SD 20 bpm), pethidine (113 SD 16 bpm) and nalbuphine (110 SD 26 bpm) was similar; with placebo HR remained faster than baseline until the seventh minute but had returned to baseline by the fifth minute with the opioids. Maximum SAP with tramadol (151 SD 26 mmHg) was similar to that with placebo (157 SD 20 mmHg), but was greater than after pethidine (136 SD 27 mmHg; p < 0.05) and nalbuphine (135 SD 19 mmHg; p < 0.02). With each test drug SAP returned to baseline by the third minute. It is concluded that, in these doses, 1) tramadol does not attenuate the chronotropic nor the inotropic response to tracheal intubation, and 2) pethidine and nalbuphine reduce only the inotropic response to airway instrumentation.
Asunto(s)
Analgésicos Opioides/farmacología , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Intubación Intratraqueal , Laringoscopía , Adulto , Analgésicos Opioides/administración & dosificación , Anestesia por Inhalación , Femenino , Humanos , Masculino , Meperidina/administración & dosificación , Meperidina/farmacología , Nalbufina/administración & dosificación , Nalbufina/farmacología , Medicación Preanestésica , Tramadol/administración & dosificación , Tramadol/farmacologíaRESUMEN
Pencil-point spinal needles are popular for combined spinal-epidural analgesia because they cause less dural puncture headache than cutting-edge spinal needles. However many parturients move, grimace, vocalise or experience paraesthesia or dysaesthesia during dural puncture when performing 'needle through needle' combined spinal-epidural analgesia. We compared dural puncture responses induced by pencil-point and cutting-edge needles (both 27 gauge). With institutional approval, 115 parturients presenting for elective caesarean section or labour analgesia were audited. After lignocaine infiltration, a Tuohy-type needle was inserted to loss of resistance to saline at a mid-lumbar interspace, and either a 27 gauge cutting-edge or 27 gauge pencil-point needle was inserted 'needle through needle' through the dura. During dural penetration, the occurrence of patient movement, grimacing or vocalisation was noted by a blinded observer, as was the patient's response to the question "Did you feel that?" asked by the anaesthetist. The audit comprised two similar groups of patients (caesarean section, n=30; labour analgesia, n=85). In both groups, grimacing and movement during thecal penetration occurred more frequently with pencil-point needles (P < 0.05 and P < 0.025, respectively). Pooled data analysis revealed that pencil-point and cutting-edge needles induced grimacing and movement in 17 (22%) and 2 (5%), spontaneous vocalisation in 4 (5%) and 1 (3%) and was perceived by 13 (17%) and 3 (8%) parturients (P < 0.025, P=NS, P=NS), respectively. Overall, 34 and 6 objective and subjective patient responses (P < 0.005) occurred when inserting these needles, respectively. Dural puncture by a 27 gauge pencil-point needle inserted 'needle through needle' when instituting combined spinal-epidural analgesia induces more iatrogenic responses than a 27 gauge cutting-edge needle.
Asunto(s)
Analgesia Obstétrica/métodos , Agujas , Punción Espinal/métodos , Adolescente , Adulto , Analgesia Epidural/métodos , Anestesia Raquidea/métodos , Cesárea , Femenino , Humanos , Trabajo de Parto , Embarazo , Estudios Prospectivos , Punción Espinal/efectos adversos , Punción Espinal/instrumentación , Adulto JovenRESUMEN
Normal saline or air is used to identify loss of resistance during identification of the epidural space for combined spinal-epidural analgesia. Following epidural needle placement using air for loss of resistance, up to 80% of parturients move, grimace, vocalise or experience paraesthesia or dysaesthesia during subsequent dural puncture by a spinal needle. We compared the effects of saline versus air for loss of resistance on the occurrence of these subjective and objective responses during thecal penetration. With institutional approval, 55 parturients presenting for labour analgesia were studied. After infiltration of lignocaine at an L2-L5 vertebral interspace, a 17 gauge Tuohy epidural needle attached to a 5 ml loss of resistance syringe containing either saline or air was inserted and advanced until loss of resistance was identified by injection of 3 to 5 ml of content. During subsequent 'needle-through-needle' insertion of a 27 gauge pencil-point spinal needle through the meninges, all subjective and objective patient responses were recorded, as well as each patient's reply to the question "Did you feel that?". The two groups (n = 28, n = 27) were comparable. In those given saline and air respectively, 5 (18%) and 12 (44%) parturients responded to and/or acknowledged having perceived dural puncture (P < 0.005). Overall, 7 and 31 (P < 0.0005) subjective and objective responses occurred during dural puncture in those given saline and air, respectively. The study found that use of saline to determine loss of resistance is associated with fewer patient responses at the moment of thecal penetration during 'needle-through-needle' placement of the spinal needle at combined spinal-epidural analgesia.