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1.
Clin Chem ; 42(5): 756-60, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8653903

RESUMO

We describe a convenient method for the separation and quantification of xanthine, hypoxanthine, and uric acid in 20 microL of cerebrospinal fluid (CSF) with use of HPLC and ultraviolet detection. The analysis is performed on a Sepharon SGX C18 column and the elution system consists of potassium phosphate buffer, pH 5.1, with 20 mL/L methanol. The lower limit of detection was 4 pmol for hypoxanthine and xanthine and 6 pmol for uric acid. Analytical recoveries of purine metabolites ranged from 98.6% to 102.9%. The intra- and interassay CVs were <3%. The applicability of the method is illustrated with the determination of micromolar concentrations of xanthine, hypoxanthine, and uric acid in CSF samples obtained from 113 patients with various neurological disorders.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Nucleotídeos de Purina/líquido cefalorraquidiano , Adulto , Isquemia Encefálica/líquido cefalorraquidiano , Cromatografia Líquida de Alta Pressão/estatística & dados numéricos , Humanos , Concentração de Íons de Hidrogênio , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Deslocamento do Disco Intervertebral/líquido cefalorraquidiano , Pessoa de Meia-Idade , Esclerose Múltipla/líquido cefalorraquidiano , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Valores de Referência , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Ácido Úrico/líquido cefalorraquidiano , Xantina , Xantinas/líquido cefalorraquidiano
2.
Acta Paediatr ; 85(4): 485-9, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8740311

RESUMO

Glial fibrillary acidic protein (GFAP) is the structural protein of the intermediate filament of astroglia. The aims of the present study were to examine GFAP in the cerebrospinal fluid (CSF) of preterm infants at different postmenstrual ages and to evaluate the potential of GFAP to predict abnormal neurodevelopmental outcome. GFAP increased in correlation with postmenstrual age in preterm infants (n = 17) and full-term infants (n = 9). The levels were five times higher in preterm infants (n = 10) with an abnormal neonatal course and/or an abnormal neurological outcome than in healthy preterm infants. The positive predictive value of a GFAP higher than the 98th percentile of normal infants was 69%, while a GFAP level below this limit invariable predicted a good outcome. Simultaneously analysed noradrenaline, hypoxanthine and glutamate did not differ between the groups. We conclude that CSF GFAP increases with maturity and that CSF GFAP appears to be a promising marker for perinatal brain damage.


Assuntos
Dano Encefálico Crônico/líquido cefalorraquidiano , Deficiências do Desenvolvimento/etiologia , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Doenças do Prematuro/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Dano Encefálico Crônico/complicações , Estudos de Casos e Controles , Feminino , Idade Gestacional , Ácido Glutâmico/líquido cefalorraquidiano , Humanos , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Recém-Nascido , Masculino , Norepinefrina/líquido cefalorraquidiano , Valor Preditivo dos Testes
3.
J Perinat Med ; 23(3): 167-74, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8568608

RESUMO

Catabolites of purine nucleotides were measured in the cerebrospinal fluid (CSF) of newborn infants with sepsis, seizures and hydrocephalus using isocratic reversed-phase HPLC. The inosine levels in the CSF of the infants with any of the illnesses were significantly higher when compared with the controls. There was a tendency for hypoxanthine levels to be higher in the group of children with hydrocephalus. No significant differences in the concentrations of xanthine, adenine and uric acid were found. The inosine concentration in the CSF is proposed to be a more sensitive indicator of brain injury than the levels of other CSF purines. The levels of all purine metabolites measured in the CSF showed large individual variations. The ratio between hypoxanthine (as an indicator of ATP breakdown) and uric acid (as a scavenger of oxygen free radicals) concentration is proposed as a new criterion to be used in the evaluation of brain injury.


Assuntos
Infecções Bacterianas/líquido cefalorraquidiano , Hidrocefalia/líquido cefalorraquidiano , Purinas/líquido cefalorraquidiano , Convulsões/líquido cefalorraquidiano , Adenina/líquido cefalorraquidiano , Infecções Bacterianas/diagnóstico , Cromatografia Líquida de Alta Pressão , Humanos , Hidrocefalia/diagnóstico , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Lactente , Recém-Nascido , Inosina/líquido cefalorraquidiano , Valor Preditivo dos Testes , Convulsões/diagnóstico , Ácido Úrico/líquido cefalorraquidiano , Xantina , Xantinas/líquido cefalorraquidiano
4.
Artigo em Alemão | MEDLINE | ID: mdl-7841274

RESUMO

OBJECTIVE: This study was carried out on cerebrospinal fluid (CSF) to investigate the perioperative course of certain ischaemic markers, namely neurone-specific enolase (NSE), creatine kinase (CK-BB), hypoxanthine, and lactate in order to identify a disturbed cerebral energy utilisation which could be responsible for the development of temporary mental dysfunctions. Those dysfunctions are characterised by preserved memory content and perception, but the coordination and association of these functions are disturbed. Typical clinical signs are motor restlessness, disordered emotions, and symptoms of dementia. Little is known about the aetiology of those symptoms, but they are most likely due to various events, such as direct drug effects, the extent of surgical trauma, sensorial deprivation, and disturbed perfusion. METHODS: Eight orthopaedic patients (ASA III or IV) scheduled for removal of their total hip replacement were anaesthetised by catheter-spinal anaesthesia (CSA) for pain relief in combination with standardised, modified neuroleptanalgesia (NLA). At six defined times (15 hours preoperatively, immediately before and after surgery and 6, 24, and 36 hours postoperatively) CSF samples were drawn and the ischaemic markers were determined by means of radioimmunoassay (NSE), electrophoresis (CK-BB), photometry (lactate), and high-pressure liquid chromatography (hypoxanthine). The release of ischaemic markers into CSF correlates linear with the extent of ischaemic brain damage. RESULTS: Mean concentrations of the following ischaemic markers increased in all patients intraoperatively: NSE from 12.3 ng/ml to 13.4 ng/ml, hypoxanthine from 1.86 mumol/l to 3.73 mumol/l, and lactate from 1.4 mmol/l to 2.0 mmol/l respectively, all of which returned to normal within 36 hours. The CK-BB concentrations were all within normal values and not affected by the operation during this investigation. CONCLUSION: Although no clinical signs of temporary mental dysfunction have been observed, the results indicate that in CSF ischaemic markers temporarily undergo certain changes in their concentrations during the removal of total hip replacements in elderly patients. These changes are reason for assuming that risk patients may suffer a temporary disturbed cerebral energy utilisation intraoperatively, even if stable clinical and cardiovascular conditions prevail under anaesthesia. Such a temporary ischaemic penumbra might be responsible for the postoperative development of temporary mental dysfunctions.


Assuntos
Isquemia Encefálica/fisiopatologia , Metabolismo Energético/fisiologia , Prótese de Quadril , Complicações Intraoperatórias/fisiopatologia , Monitorização Intraoperatória , Transtornos Neurocognitivos/fisiopatologia , Idoso , Raquianestesia , Barreira Hematoencefálica/fisiologia , Isquemia Encefálica/prevenção & controle , Creatina Quinase/líquido cefalorraquidiano , Demência Vascular/fisiopatologia , Demência Vascular/prevenção & controle , Feminino , Humanos , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Complicações Intraoperatórias/prevenção & controle , Lactatos/líquido cefalorraquidiano , Ácido Láctico , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/prevenção & controle , Neuroleptanalgesia , Fosfopiruvato Hidratase/líquido cefalorraquidiano , Reoperação
5.
Am J Obstet Gynecol ; 169(6): 1493-501, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8267052

RESUMO

OBJECTIVE: Our purpose was to study the effect of fetal asphyxia on the release of hypoxanthine and xanthine in cerebrospinal fluid and on brain histologic characteristics. STUDY DESIGN: In seven fetal lambs (3 to 5 days after surgery, gestational age 124.3 +/- 2.6 days) asphyxia was induced by restriction of uterine blood flow. RESULTS: Fetal pH and base excess were reduced to 6.99 +/- 0.02 and -17.6 +/- 0.9 mmol/L, respectively. Cerebral blood flow increased during asphyxia and returned to normal in the recovery phase. Maximum concentrations of cerebrospinal fluid hypoxanthine and xanthine were reached in the normoxemic recovery phase. This high level of substrates during normoxemia facilitates oxygen free radical formation and may thus aggravate postasphyctic brain damage. Histologic evaluation of the brain 3 days after the insult showed a variable degree of edema. Coagulative neuronal changes, characteristic of irreversible cell death, were only occasionally detected. These changes were most obvious in the Purkinje cells of the cerebellum. CONCLUSIONS: Fetal asphyxia induced by uterine blood flow restriction is associated with high levels of cerebrospinal fluid hypoxanthine and xanthine in the recovery phase. Microscopically detectable brain damage, although not extensive, is mainly located in the cerebellum.


Assuntos
Encéfalo/patologia , Circulação Cerebrovascular/fisiologia , Hipóxia Fetal/fisiopatologia , Animais , Pressão Sanguínea , Edema Encefálico/etiologia , Edema Encefálico/patologia , Cerebelo/patologia , Feminino , Hipóxia Fetal/metabolismo , Hipóxia Fetal/patologia , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Lactatos/líquido cefalorraquidiano , Ácido Láctico , Oxigênio/sangue , Gravidez , Ovinos , Xantina , Xantinas/líquido cefalorraquidiano
6.
Acta Paediatr ; 82(10): 849-52, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8241644

RESUMO

The release of agents mediating inflammation in meningitis may bring about neuronal hypoxia, under which circumstances ATP concentrations decrease and its degradation products increase and are released into the cerebrospinal fluid. In this study of alterations in neuronal energy metabolism in meningitis, AMP, IMP, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and urate were determined by high performance liquid chromatography in the cerebrospinal fluid of 54 children aged between 1 month and 13 years suffering from meningitis (25 viral, 24 bacterial and 5 tuberculous cases) and 63 controls. Compared to the controls, patients with viral meningitis exhibited high concentrations of IMP, adenosine, guanosine, adenine, guanine and xanthine; patients with bacterial meningitis exhibited high concentrations of IMP, inosine, guanosine, adenosine, hypoxanthine, xanthine and urate; and patients with tuberculous meningitis exhibited high concentrations of AMP, guanosine, xanthine and urate. Viral and bacterial cases did not differ significantly for any of the metabolites studied. AMP and urate concentrations were significantly higher in patients with tuberculous cases compared with viral or bacterial meningitis cases.


Assuntos
Meningite/líquido cefalorraquidiano , Nucleosídeos/líquido cefalorraquidiano , Nucleotídeos/líquido cefalorraquidiano , Ácido Úrico/líquido cefalorraquidiano , Monofosfato de Adenosina/líquido cefalorraquidiano , Trifosfato de Adenosina/líquido cefalorraquidiano , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Lactente , Recém-Nascido , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningite Viral/líquido cefalorraquidiano , Tuberculose Meníngea/líquido cefalorraquidiano , Xantina , Xantinas/líquido cefalorraquidiano
7.
Childs Nerv Syst ; 9(5): 275-7, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8252517

RESUMO

We used high performance liquid chromatography to determine the concentration of purine metabolites in the cerebrospinal fluid of three hydrocephalic children with a history of shunt malfunction. Hypoxanthine and xanthine levels were high in comparison with controls. We consider these purines to be valuable indicators of disturbance of neuronal metabolism following the sustained rise in intracranial pressure caused by shunt valve malfunction.


Assuntos
Derivações do Líquido Cefalorraquidiano , Hidrocefalia/cirurgia , Hipóxia/líquido cefalorraquidiano , Complicações Pós-Operatórias/líquido cefalorraquidiano , Purinas/líquido cefalorraquidiano , Adolescente , Adulto , Criança , Pré-Escolar , Falha de Equipamento , Feminino , Humanos , Hidrocefalia/líquido cefalorraquidiano , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Lactente , Masculino , Xantina , Xantinas/líquido cefalorraquidiano
8.
J Clin Pathol ; 46(7): 650-3, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8157754

RESUMO

AIMS: To assess the rate at which premortem hypoxia occurs in sudden infant death syndrome (SIDS) when compared with death in early childhood. METHODS: The hypoxanthine concentration was measured as a marker of premortem hypoxia in vitreous humour and cerebrospinal fluid samples obtained at necropsy from 119 children whose ages ranged from 1 week to 2 years. RESULTS: Increasing interval between death and necropsy was accompanied by an increase in the hypoxanthine concentration of vitreous humour for the first 24 hours, at a rate of 8.3 mumol/l/hour. Thereafter, there was little change with time, and the results wer corrected to 24 hours according to a regression equation. Cerebrospinal fluid concentrations showed no significant change with time following death. Patients were divided into three groups according to the cause of death: SIDS, cardiac or pulmonary disease, and others. Median values for the cerebrospinal fluid hypoxanthine concentrations were not significantly different among the groups and no difference could be shown between the vitreous humour hypoxanthine concentration in cases of SIDS and those children dying from other causes. Patients with established cardiac or pulmonary disease had a significantly reduced vitreous humour hypoxanthine concentration which may have reflected the premortem use of artificial ventilation. CONCLUSIONS: The results of this study do not support the view that pre-mortem hypoxia is a common feature in SIDS when compared with other causes of death.


Assuntos
Hipoxantinas/análise , Hipóxia/metabolismo , Morte Súbita do Lactente/etiologia , Corpo Vítreo/química , Biomarcadores/análise , Biomarcadores/líquido cefalorraquidiano , Humanos , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Hipóxia/líquido cefalorraquidiano , Lactente , Recém-Nascido , Mudanças Depois da Morte , Análise de Regressão , Morte Súbita do Lactente/líquido cefalorraquidiano , Fatores de Tempo
9.
J Cereb Blood Flow Metab ; 13(2): 214-20, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8436613

RESUMO

We measured the changes in pial arteriolar diameter and CSF concentrations of adenosine, inosine, and hypoxanthine during hypoxia in the absence and presence of topically applied dipyridamole (10(-6) M) and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; 10(-5) M). Closed cranial windows were implanted in halothane-anesthetized adult male Sprague-Dawley rats for the observation of the pial circulation and collection of CSF. The mean resting arteriolar diameter in mock CSF was 31.2 +/- 5.9 microns. Topically applied dipyridamole and EHNA, in combination, caused a slight but significant (p < 0.05) increase in resting arteriolar diameter (33.8 +/- 4.3 microns). With mock CSF, moderate hypoxia caused a 22.1 +/- 9.7% increase in pial vessel diameter. Topically applied dipyridamole and EHNA significantly (p < 0.01) potentiated pial arteriolar vasodilation in response to hypoxia. Moreover, the potentiating effects of dipyridamole and EHNA during hypoxia were completely abolished by theophylline (0.20 mumol/g, i.p.; p < 0.05), an adenosine receptor antagonist. Resting concentrations of adenosine, inosine, and hypoxanthine in the subwindow CSF were 0.18 +/- 0.09, 0.35 +/- 0.21, and 0.62 +/- 0.12 microM, respectively. In the absence of dipyridamole and EHNA, these levels were not affected by sustained moderate hypoxia (PaO2 = 36 +/- 6 mm Hg). However, in the presence of dipyridamole and EHNA, the concentration of adenosine in the CSF during hypoxia was significantly (p < 0.05) increased. Our data indicate that dipyridamole and EHNA potentiate hypoxic vasodilation of pial arterioles while simultaneously increasing extracellular adenosine levels, thus supporting the hypothesis that adenosine is involved in the regulation of cerebral blood flow.


Assuntos
Adenina/análogos & derivados , Adenosina/líquido cefalorraquidiano , Dipiridamol/farmacologia , Hipóxia/líquido cefalorraquidiano , Pia-Máter/irrigação sanguínea , Adenina/farmacologia , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/patologia , Circulação Cerebrovascular , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Hipóxia/patologia , Hipóxia/fisiopatologia , Inosina/líquido cefalorraquidiano , Masculino , Pia-Máter/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacos
10.
J Perinat Med ; 21(3): 211-7, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8229612

RESUMO

To determine whether an elevated level of hypoxanthine in cerebrospinal fluid or vitreous humor might reflect a high plasma hypoxanthine concentration, or whether it necessarily represents local tissue hypoxia, we infused hypoxanthine intravenously to normoxemic and normotensive piglets (n = 6). Hypoxanthine was measured in different body fluids using HPLC. During the 8 hours of infusion hypoxanthine increased in plasma (from 30 +/- 6 mumol/l (mean +/- SD) before the infusion to 68 +/- 20 mumol/l at the end of the infusion, p < 0.01), cerebrospinal fluid (CSF) (19 +/- 8 to 43 +/- 9 mumol/l, p < 0.05) and vitreous humor (15 +/- 5 to 30 +/- 6 mumol/l, p < 0.05). After infusion, hypoxanthine values in all three fluids were similar to those seen in pigs after severe hypoxia. Hypoxanthine in vitreous humor and plasma were significantly correlated (r = 0.80, 95% confidence interval 0.47-0.93, p < 0.001). Urinary excretion of hypoxanthine increased almost 40 times from 0.12 +/- 0.14 to 4.6 +/- 2.9 mumol/kg/h indicating that renal excretion of hypoxanthine is not achieved just by passive filtration. We conclude that in newborn piglets hypoxanthine can pass from plasma to CSF and vitreous humor. Thus an increased CSF hypoxanthine concentration is not definite proof that significant cerebral hypoxia has occurred.


Assuntos
Animais Recém-Nascidos/metabolismo , Hipoxantinas/sangue , Hipoxantinas/líquido cefalorraquidiano , Corpo Vítreo/metabolismo , Animais , Transporte Biológico , Cromatografia Líquida de Alta Pressão , Hipoxantina , Hipoxantinas/metabolismo , Cinética , Suínos , Ácido Úrico/sangue , Ácido Úrico/líquido cefalorraquidiano , Ácido Úrico/metabolismo , Xantina , Xantinas/sangue , Xantinas/líquido cefalorraquidiano , Xantinas/metabolismo
11.
Pediatr Res ; 32(1): 107-13, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1635835

RESUMO

To study whether room air is as effective as 100% O2 in resuscitation after hypoxia, hypoxemia (PaO2 2.3-4.3 kPa) was induced in newborn pigs (2-5 d old) by ventilation with 8% O2 in nitrogen. When systolic blood pressure had fallen to 20 mm Hg, animals were randomly reoxygenated with either 21% O2 (group 1, n = 9) or 100% O2 (group 2, n = 11) for 20 min followed by 21% O2 in both groups. Controls (group 3, n = 5) were ventilated with 21% O2 throughout the experiment. Base deficit peaked at 31 +/- 5 mmol/L (mean +/- SD) for both hypoxic groups at 5 min of reoxygenation and then normalized over the following 3 h. There were no statistically significant differences between the two groups during reoxygenation concerning blood pressure, heart rate, base deficit, or plasma hypoxanthine. Hypoxanthine peaked at 165 +/- 40 and 143 +/- 42 mumol/L in group 1 and 2 (NS), respectively, and was eliminated monoexponentially in both groups with an initial half-life for excess hypoxanthine of 48 +/- 21 and 51 +/- 27 min (NS), respectively. Blinded pathologic examination of cerebral cortex, cerebellum, and hippocampus after 4 d showed no statistically significant differences with regard to brain damage. We conclude that 21% O2 is as effective as 100% O2 for normalizing blood pressure, heart rate, base deficit, and plasma hypoxanthine after severe neonatal hypoxemia in piglets and that the extent of the hypoxic brain damage is similar in the two groups.


Assuntos
Hipóxia/terapia , Oxigênio , Animais , Animais Recém-Nascidos , Glicemia/metabolismo , Pressão Sanguínea , Encéfalo/patologia , Frequência Cardíaca , Concentração de Íons de Hidrogênio , Hipoxantina , Hipoxantinas/sangue , Hipoxantinas/líquido cefalorraquidiano , Hipóxia/patologia , Hipóxia/fisiopatologia , Hipóxia Encefálica/patologia , Suínos
12.
J Cereb Blood Flow Metab ; 11(6): 986-93, 1991 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1939392

RESUMO

We utilized the closed cranial window technique in the anesthetized rat to determine changes in CSF concentrations of adenosine, inosine, and hypoxanthine and pial arteriolar diameter during transient (20 min) forebrain ischemia and reperfusion. After mock CSF under the cranial window was allowed to equilibrate with cerebral interstitial fluid, endogenous adenosine concentration was found to be 0.16 +/- 0.05 microM, while inosine and hypoxanthine were 0.35 +/- 0.17 and 1.23 +/- 0.47 microM, respectively. The concentration of adenosine in CSF increased 4.2-fold during ischemia and 13.8-fold during the first 5 min of reperfusion. Inosine and hypoxanthine concentrations were also significantly increased during ischemia and reperfusion. After 1 h of reperfusion, CSF adenosine and inosine levels had decreased from peak value but remained significantly above preischemic values. In contrast, hypoxanthine remained at peak concentrations even after 60 min of reperfusion. Preischemic arteriolar diameter was 42.6 +/- 11.3 microns and was not significantly changed after 20 min of ischemia. However, during the first 5 min of reperfusion, arteriolar diameter increased significantly (p less than 0.05), coincident with peak adenosine concentrations. By 60 min of reperfusion, arteriolar diameter had returned to baseline. These results indicate that during the postischemic period, adenine nucleosides and hypoxanthine in CSF are elevated and could affect reperfusion.


Assuntos
Adenosina/líquido cefalorraquidiano , Arteríolas/fisiopatologia , Ataque Isquêmico Transitório/líquido cefalorraquidiano , Pia-Máter/irrigação sanguínea , Animais , Circulação Cerebrovascular , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Inosina/líquido cefalorraquidiano , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Ratos , Ratos Endogâmicos , Vasodilatação
13.
Dev Med Child Neurol ; 33(10): 908-11, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1743415

RESUMO

Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid and pyrimidine bases were determined in the CSF of 18 children after simple febrile seizures and in a control group. There was no statistically significant difference between the two groups for any of these metabolites. This suggests that simple febrile seizures neither significantly disturb the metabolism of nucleotides, nucleosides or bases, nor significantly deplete neuron adenosine triphosphate ATP levels.


Assuntos
Purinas/líquido cefalorraquidiano , Nucleosídeos de Pirimidina/líquido cefalorraquidiano , Convulsões Febris/líquido cefalorraquidiano , Adenina/líquido cefalorraquidiano , Adenosina/líquido cefalorraquidiano , Monofosfato de Adenosina/líquido cefalorraquidiano , Pré-Escolar , Citosina/líquido cefalorraquidiano , Feminino , Guanina/líquido cefalorraquidiano , Guanosina/líquido cefalorraquidiano , Humanos , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Lactente , Inosina/líquido cefalorraquidiano , Inosina Monofosfato/líquido cefalorraquidiano , Masculino , Timina/líquido cefalorraquidiano , Uracila/líquido cefalorraquidiano , Ácido Úrico/líquido cefalorraquidiano , Xantina , Xantinas/líquido cefalorraquidiano
14.
Am J Physiol ; 261(2 Pt 2): H398-403, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1877666

RESUMO

We hypothesized that systemic hyperglycemia would alter cerebral adenosine concentrations during ischemia and reperfusion. In the present study, we analyzed brain tissue and cerebrospinal fluid (CSF) from hyperglycemic and normoglycemic rats before ischemia, after 15 min of incomplete forebrain ischemia, and during 60 min of reperfusion. Hyperglycemic rats received 3 g/kg of 17% D-glucose intraperitoneally, which increased blood glucose to 357 +/- 23 mg/100 ml compared with 128 +/- 12 mg/100 ml in normoglycemic rats. Brain tissue was sampled by the freeze-blow technique, and CSF was obtained by collecting cortical perfusate from the closed cranial window. Tissue and CSF were analyzed for adenosine and its metabolites inosine and hypoxanthine, and tissue was also analyzed for adenine nucleotides. Hyperglycemia significantly attenuated the increase in brain tissue and CSF adenosine and its metabolites during ischemia while preserving adenine nucleotide concentrates. This attenuation of ischemic adenosine production persisted after 5 min of reperfusion in tissue and throughout 60 min of reperfusion in CSF. Because adenosine, a cerebral vasodilator, can inhibit the release of neuronal excitotoxins as well as affect neutrophil-endothelial interactions, adenosine has been proposed as an endogenous neuroprotector. Thus the attenuation of adenosine and its metabolites may be a factor in the pathogenesis of increased ischemic brain injury associated with systemic hyperglycemia.


Assuntos
Adenosina/biossíntese , Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Hiperglicemia/metabolismo , Reperfusão , Nucleotídeos de Adenina/metabolismo , Adenosina/líquido cefalorraquidiano , Animais , Encéfalo/irrigação sanguínea , Isquemia Encefálica/líquido cefalorraquidiano , Hiperglicemia/líquido cefalorraquidiano , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Hipoxantinas/metabolismo , Inosina/líquido cefalorraquidiano , Inosina/metabolismo , Masculino , Ratos , Ratos Endogâmicos
15.
J Cereb Blood Flow Metab ; 11(3): 424-31, 1991 May.
Artigo em Inglês | MEDLINE | ID: mdl-2016349

RESUMO

This study investigated the potential role of adenosine in cerebral blood flow (CBF) regulation in the neonate during moderate and severe hypotension. Experiments were done in anesthetized, 1- to 3-day-old piglets. Regional CBF (determined by radiolabeled microsphere technique) and cerebral metabolic rate for O2 (CMRO2) were measured (a) during normotension and (b) during a 3-min period of moderate (58 +/- 9 mm Hg) or severe (36 +/- 7 mm Hg) hypotension produced by the inflation of a balloon catheter placed in the aortic root. Measurements of CBF and CMRO2 were performed successively after intracerebroventricular (i.c.v.) injections of vehicle (n = 17), the adenosine receptor blocker 8-phenyltheophylline (8-PT, 10 micrograms, n = 14), and the A2-receptor agonist 5'-N-(ethylcarboxamide)adenosine (NECA, 2 ng, n = 8). After i.c.v. administration of vehicle, none of the parameters studied was significantly altered by moderate hypotension, but severe hypotension decreased the total CBF (mean +/- SD) from 86 +/- 24 to 40 +/- 15 ml min-1 100 g-1 and CMRO2 from 3.2 +/- 0.8 to 1.8 +/- 1.0 ml min-1 100 g-1 (p less than 0.05). Administration of 8-PT did not alter these parameters during normotension, but significantly decreased CBF during moderate hypotension compared to postvehicle values (53 +/- 11 versus 81 +/- 12 ml min-1 100 g-1, p less than 0.05). This loss of autoregulation was completely reversed by NECA. During severe hypotension, 8-PT altered the CBF redistribution towards the brainstem.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Adenosina/fisiologia , Animais Recém-Nascidos/fisiologia , Circulação Cerebrovascular/fisiologia , Hipotensão/fisiopatologia , Adenosina/análogos & derivados , Adenosina/líquido cefalorraquidiano , Adenosina/farmacologia , Adenosina-5'-(N-etilcarboxamida) , Animais , Velocidade do Fluxo Sanguíneo , Encéfalo/metabolismo , Circulação Cerebrovascular/efeitos dos fármacos , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Inosina/líquido cefalorraquidiano , Oxigênio/metabolismo , Receptores Purinérgicos/efeitos dos fármacos , Receptores Purinérgicos/fisiologia , Suínos , Teofilina/análogos & derivados , Teofilina/farmacologia , Resistência Vascular/fisiologia
16.
Res Exp Med (Berl) ; 191(3): 219-25, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1925070

RESUMO

This investigation was designed to study the dynamics of energy-related metabolites (i.e., lactate, pyruvate, inosine, and hypoxanthine) in the extracellular fluid (ECF) of the striatum and in cisternal cerebrospinal fluid (CSF) during the first 6 h after middle cerebral artery occlusion (MCAO) using microdialysis. Ischemia induced a dramatic increase in the ECF levels of lactate, inosine, and hypoxanthine, while pyruvate did not change significantly. The major part of these changes occurred during the first 10 min after MCAO. Inosine tended to normalize towards the end, while lactate and hypoxanthine remained elevated throughout the experiment. There was no increase of the energy-related metabolites in CSF during the experiment. It was concluded that lactate, inosine, and hypoxanthine appear to be useful ECF markers of the compromised energy state of the brain during ischemia. Because the metabolites did not appear in CSF during the first 6 h after MCAO, such measurements seem not to be useful for early detection of a disturbance in energy metabolism.


Assuntos
Isquemia Encefálica/metabolismo , Metabolismo Energético , Animais , Arteriopatias Oclusivas/líquido cefalorraquidiano , Arteriopatias Oclusivas/metabolismo , Isquemia Encefálica/líquido cefalorraquidiano , Artérias Cerebrais , Espaço Extracelular/metabolismo , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Hipoxantinas/metabolismo , Inosina/líquido cefalorraquidiano , Inosina/metabolismo , Lactatos/líquido cefalorraquidiano , Lactatos/metabolismo , Ácido Láctico , Masculino , Piruvatos/líquido cefalorraquidiano , Piruvatos/metabolismo , Ácido Pirúvico , Ratos , Ratos Endogâmicos
18.
Psychoneuroendocrinology ; 16(4): 311-22, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1720895

RESUMO

Psychiatric disturbances are common in primary hyperparathyroidism (HPT), but their pathogenesis is essentially unknown. This study deals with cerebrospinal fluid (CSF) calcium homeostasis and its connection with parathyroid hormone (PTH), blood-brain barrier (BBB) function, and central monoamine and purine metabolites in patients with primary HPT. In 22 patients with primary HPT (serum calcium 2.85 +/- 0.21 mmol/l), the CSF concentrations of total and ionized calcium were higher (1.21 +/- 0.08 mmol/l, p less than 0.01, and 1.09 +/- 0.05 mmol/l, p less than 0.001, respectively) than in 11 normocalcemic reference subjects. The values correlated with serum calcium concentration (p less than 0.001) and CSF/serum albumin ratio, a measure of BBB permeability. The latter ratio was elevated in one-third of the patients with HPT, indicating BBB damage. CSF immunoreactive intact PTH was higher in the HPT patients than in the reference group (p less than 0.05), and serum and CSF PTH were positively correlated (p less than 0.05). The CSF levels of the monoamine metabolites 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were lower, and the level of urate in CSF was higher, in the HPT patients than in the reference subjects, while there were no consistent differences in CSF hypoxanthine or xanthine. CSF 5HIAA correlated inversely with CSF ionized calcium (r = -0.42, p = 0.02). After parathyroid surgery, CSF calcium and urate decreased significantly and CSF monoamine metabolites increased slightly. The decrease in CSF ionized calcium correlated with the alleviation of psychiatric symptoms. The results indicate the importance of increased CSF calcium concentrations in patients with primary HPT and suggest a relation between central calcium regulation and central turnover of monoamines.


Assuntos
Barreira Hematoencefálica/fisiologia , Cálcio/líquido cefalorraquidiano , Ácido Homovanílico/líquido cefalorraquidiano , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Hiperparatireoidismo/fisiopatologia , Hipoxantinas/líquido cefalorraquidiano , Metoxi-Hidroxifenilglicol/líquido cefalorraquidiano , Transtornos Neurocognitivos/fisiopatologia , Hormônio Paratireóideo/líquido cefalorraquidiano , Xantinas/líquido cefalorraquidiano , Humanos , Hiperparatireoidismo/psicologia , Hipoxantina , Transtornos Neurocognitivos/psicologia , Glândulas Paratireoides/fisiopatologia , Albumina Sérica/líquido cefalorraquidiano , Xantina
19.
Cell Mol Neurobiol ; 10(3): 327-36, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2253261

RESUMO

1. Rats which survived hypoglycemia by insulin, hypoxia by 10% O2, or ischemia by carotid ligation and hypotension to 40 mm Hg, evidenced no changes in cerebrospinal fluid (CSF) uridine. Animals which died soon after the above interventions or as a result of KCl-induced cardiac arrest had elevated CSF uridine concentrations. 2. Injection of whole blood or the soluble contents of lysed blood cells into the lateral ventricle of rats reduced CSF uridine to less than one-half normal at 24 hrs but values returned to normal 3 days later. Changes in hypoxanthine resembled those of uridine, but were less dramatic, whereas xanthine concentrations were largely unaltered. Intraventricular injection of plasma or saline did not alter CSF uridine. 3. It seems most likely that low CSF uridine concentrations previously reported in head injury patients may be secondary to the effects of blood cell contents in the cerebrospinal fluid, rather than responses to altered metabolism in neurons or glia cells.


Assuntos
Sangue , Isquemia Encefálica/líquido cefalorraquidiano , Uridina/líquido cefalorraquidiano , Animais , Parada Cardíaca/líquido cefalorraquidiano , Parada Cardíaca/induzido quimicamente , Hipoglicemia/líquido cefalorraquidiano , Hipoglicemia/induzido quimicamente , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Hipóxia/líquido cefalorraquidiano , Injeções Espinhais , Insulina/toxicidade , Mudanças Depois da Morte , Cloreto de Potássio/toxicidade , Ratos , Ratos Endogâmicos , Xantina , Xantinas/líquido cefalorraquidiano
20.
J Appl Physiol (1985) ; 68(4): 1534-41, 1990 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2347792

RESUMO

This study investigated the role of adenosine in the regulation of neonatal cerebral blood flow (CBF) during moderate (arterial PO2 = 47 +/- 9 Torr) and severe (arterial PO2 = 25 +/- 4 Torr) hypoxia. Twenty-eight anesthetized and ventilated newborn piglets were assigned to four groups: 8 were injected intravenously with the vehicle (controls, group 1); 13 received an intravenous injection of 8-phenyltheophylline (8-PT), a potent adenosine receptor blocker, either 4 mg/kg (group 2, n = 6, mean cerebrospinal fluid (CSF) levels less than 1 mg/l) or 8 mg/kg (group 3, n = 7, mean CSF levels less than 3.5 mg/l); and 7 received an intracerebroventricular injection of 10 micrograms 8-PT (group 4). During normoxia, CBF was not altered by vehicle or 8-PT injections. In group 1, 10 min of moderate and severe hypoxia increased total CBF by 112 +/- 36 and 176 +/- 28% (SE), respectively. Compared with controls, the cerebral hyperemia during moderate hypoxia was not altered in group 2, attenuated in group 3 (to 53 +/- 13%, P = NS), and completely blocked in group 4 (P less than 0.01). CBF increase secondary to severe hypoxia was attenuated only in group 4 (74 +/- 29%, P less than 0.05). CSF concentrations of adenosine and adenosine metabolites measured by high-performance liquid chromatography increased during hypoxia. Arterial O2 content was inversely correlated (P less than 0.005) to maximal CSF levels of adenosine (r = 0.73), inosine (r = 0.87), and hypoxanthine (r = 0.80).(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Animais Recém-Nascidos/fisiologia , Circulação Cerebrovascular , Hipóxia/fisiopatologia , Adenosina/antagonistas & inibidores , Adenosina/líquido cefalorraquidiano , Adenosina/fisiologia , Animais , Artérias , Circulação Cerebrovascular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Hipoxantina , Hipoxantinas/líquido cefalorraquidiano , Injeções Intraventriculares , Inosina/líquido cefalorraquidiano , Oxigênio/sangue , Suínos , Teofilina/administração & dosagem , Teofilina/análogos & derivados , Teofilina/líquido cefalorraquidiano , Teofilina/farmacologia , Resistência Vascular
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