RESUMO
Transmembrane alanine transport was studied in hepatocytes isolated from 48-h fasted rats. Aminooxyacetate was used to render alanine nonmetabolizable. Gramicidin D eliminated the transmembrane Na+ electrochemical gradient. At 135 mM Na+ and 0.1 mM alanine gramicidin D decreased the steady-state intracellular-to-extracellular alanine distribution ratio from 20.2 to 0.9. The underlying kinetic changes appeared to be a decrease in alanine influx to one-third of the control value and an increase in the rate constant of alanine efflux by a factor of 9. Analogous changes were observed when the Na+ gradient was decreased by ouabain. The inhibitory effect of gramicidin D on alanine influx was confined to the Na+-dependent, saturable component which showed a prominent increase in the apparent Km for alanine and a small decrease in the apparent Vmax. The effect of gramicidin D on alanine efflux was related to the increased cytosolic Na+ concentration: the rate constant of alanine efflux was increased by cytosolic Na+ with half-maximal stimulation at 30 mM; voltage-sensitive alanine efflux could not be demonstrated.
Assuntos
Alanina/metabolismo , Fígado/metabolismo , Sódio/metabolismo , Animais , Eletroquímica , Feminino , Gramicidina/farmacologia , Cinética , Potenciais da Membrana , Ouabaína/farmacologia , Ratos , Ratos Endogâmicos , Valinomicina/farmacologiaRESUMO
The mechanism of liver glycogen synthesis after refeeding has been investigated in diabetic rats, diabetic insulin-treated rats, and in control rats fasted for 48 h. The accumulation of liver glycogen was the same in diabetic rats and in control rats after 2 h of feeding, but did not proceed any further in the diabetic group during the next 2 h. Insulin-treated diabetic rats synthesized five times more hepatic glycogen than the control rats after 1 h of refeeding, but the amount accumulated at the end of the refeeding period was the same. Feeding resulted in a transient activation of glycogen synthase in untreated as well as in treated diabetic rats. In control rats, however, glycogen synthase was already partially in the active form before access to food, and the onset of glycogen synthesis occurred without further activation of the enzyme. A transient inactivation of phosphorylase was observed in all groups during the meal, but was very slight in the untreated diabetic rats in which phosphorylase a values were already reduced before the access to food. Peripheral glycemia was markedly increased upon refeeding in treated and untreated diabetic rats, but remained normal in control rats. Peripheral insulinemia was increased by feeding in the control rats and remained low in the diabetic rats and high in the insulin-treated diabetic rats. The results indicate that, in normal controls in contrast to diabetic rats, synthase activation is not a prerequisite for the initiation of glycogen synthesis after a meal; phosphorylase inactivation may be of major importance in normal controls, but also appears to play a role in the diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Diabetes Mellitus Experimental/metabolismo , Insulina/farmacologia , Glicogênio Hepático/biossíntese , Animais , Ingestão de Alimentos , Jejum , Feminino , Glicogênio Sintase/metabolismo , Insulina/sangue , Fosforilases/metabolismo , Ratos , Ratos EndogâmicosRESUMO
BACKGROUND: Antimyosin Fab fragment has been shown to bind to myosin leaked from necrotic cardiac cells but not to myosin in undamaged cells. The purpose of this investigation was to evaluate indium 111-antimyosin Fab fragment scintigraphy as a noninvasive technique in the diagnosis of acute rejection after heart transplantation. Simultaneous endomyocardial biopsy served as the gold standard. METHODS: Twenty-two patients had scintigraphic studies at weeks 3 to 4, 6, 10, 26, and 52, but the next 16 patients underwent scintigraphy more often, that is, at all scheduled biopsies performed from week 3 to week 26 after transplantation. From analysis of the first 70 studies, an interstudy decrease in the patient's heart-to-lung ratio was classified as normal, that is, no rejection, whereas an unchanged or increased heart-to-lung ratio was considered pathologic. RESULTS: By use of this definition of negative and positive scintigraphic results, prospective analysis of 88 conclusive, consecutive studies showed 6 true- and 31 false-positive studies (prevalence of rejection 8%), giving a low predictive value of a pathologic change in heart-to-lung ratio. Of the 51 studies with decreasing heart-to-lung ratio only 1 was a false negative, giving a predictive value of a negative study of 98% (95% confidence limits 90% to 100%). CONCLUSIONS: In conclusion, antimyosin scintigraphy is a promising noninvasive technique in the routine surveillance of acute heart rejection. Because of many false-positive results in the studies, biopsy should be used as a control for a pathologic heart-to-lung ratio.
Assuntos
Anticorpos Monoclonais , Rejeição de Enxerto/diagnóstico por imagem , Transplante de Coração/diagnóstico por imagem , Radioisótopos de Índio , Miosinas/imunologia , Compostos Organometálicos , Doença Aguda , Adulto , Biópsia , Endocárdio/patologia , Reações Falso-Positivas , Feminino , Rejeição de Enxerto/patologia , Transplante de Coração/imunologia , Transplante de Coração/patologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Miocárdio/patologia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Estudos Prospectivos , Cintilografia , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
Respiratory failure can be difficult to predict. It can develop into a life-threatening condition in just a few minutes, or it can build up more slowly. Thus continuous monitoring of respiratory activity should be mandatory in clinical, high-risk situations, and appropriate monitoring equipment could be life-saving. The review considers non-invasive methods and devices claimed to provide information about respiratory rate or depth, or gas exchange. Methods are categorised into those responding to movement, volume and tissue composition detection; air flow; and blood gas concentration. The merits and limitations of the methods and devices are analysed, considering information content and their ability to minimise the rate of false alarms and false non-alarms. It is concluded that the field of non-invasive respiratory monitoring is still in an exploratory phase, with numerous reports on specific device solutions but less work on evaluation and adaptation to clinical requirements. Convincing evidence of the clinical usefulness of respiratory monitors is still lacking. Devices responding only to respiratory rate, and lacking information about actual gas exchange, will have limited clinical value. Furthermore, enhancement in specificity and sensitivity to avoid false alarms and non-alarms will be necessary to meet clinical requirements. Miniature CO2 sensors are identified as one route towards substantial improvement.
Assuntos
Cuidados Críticos/métodos , Pulmão/fisiopatologia , Monitorização Fisiológica/métodos , Insuficiência Respiratória/diagnóstico , Testes Respiratórios , Dióxido de Carbono/análise , Humanos , Monitorização Fisiológica/instrumentação , Oximetria , Oxigênio/análise , Pletismografia , Músculos Respiratórios/fisiopatologiaRESUMO
Preoperative bone scintigraphy of the femoral head in 33 hips with slipped capital femoral epiphysis, showed no relation to duration of symptoms or degree of slip. The preoperative uptake was always normal or increased. Two hips had postoperative femoral head uptake below normal, both had complications affecting the vascular supply, resulting in necrosis of the femoral head and severe arthrosis. At follow-up after 10 (5-15) years of 28 hips, no relation could be demonstrated between Adolescent Hip Questionnaire which included clinical data, and radiography or magnetic resonance imaging. We only recommend scintigraphy after complications jeopardizing the vascular supply of the femoral head in slipped capital femoral epiphysis.
Assuntos
Epifise Deslocada/diagnóstico por imagem , Cabeça do Fêmur/diagnóstico por imagem , Adolescente , Criança , Epifise Deslocada/patologia , Epifise Deslocada/cirurgia , Feminino , Cabeça do Fêmur/irrigação sanguínea , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia , Cintilografia , Resultado do TratamentoAssuntos
Glicerol/metabolismo , Hipertireoidismo/fisiopatologia , Hipotireoidismo/fisiopatologia , Fígado/fisiologia , Potenciais da Membrana , Glândula Tireoide/fisiologia , Trifosfato de Adenosina/biossíntese , Animais , Membrana Celular/metabolismo , Feminino , Glicerofosfatos/biossíntese , Fígado/metabolismo , Fígado/fisiopatologia , Consumo de Oxigênio , Perfusão , Fósforo/metabolismo , Potássio/metabolismo , RatosAssuntos
Metabolismo Energético , Gluconeogênese , Glicerol/metabolismo , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Fígado/metabolismo , Glândula Tireoide/fisiologia , Acetoacetatos/metabolismo , Animais , Peso Corporal , Metabolismo Energético/efeitos dos fármacos , Feminino , Gluconeogênese/efeitos dos fármacos , Glicerol/farmacologia , Hidroxibutiratos/metabolismo , Hipertireoidismo/induzido quimicamente , Hipotireoidismo/induzido quimicamente , Iodo , Lactatos/metabolismo , Fígado/efeitos dos fármacos , Tamanho do Órgão , Perfusão , Piruvatos/metabolismo , Ratos , Tri-IodotironinaRESUMO
The aim of this study was to validate a non-invasive optical probe for simultaneous blood flow measurement at different vascular depths combining three photoplethysmography (PPG) channels and laser Doppler flowmeter (LDF). Wavelengths of the PPG were near-infrared 810 nm with source-to-detector separation of 10 and 25 mm, and green 560 nm with source-to-detector separation of 4 mm. The probe is intended for clinical studies of pressure ulcer aetiology. The probe was placed over the trapezius muscle, and depths from the skin to the trapezius muscle were measured using ultrasound and varied between 3.8 and 23 mm in the 11 subjects included. A provocation procedure inducing a local enhancement of blood flow in the trapezius muscle was used. Blood flows at rest and post-exercise were compared. It can be concluded that this probe is useful as a tool for discriminating between blood flows at different vascular tissue depths. The vascular depths reached for the different channels in this study were at least 23 mm for the near-infrared PPG channel (source-to-detector separation 25 mm), 10-15 mm for the near-infrared PPG channel (separation 10 mm), and shallower than 4 mm for both the green PPG channel (separation 4 mm) and LDF.
Assuntos
Fluxometria por Laser-Doppler/métodos , Músculo Esquelético/irrigação sanguínea , Fotopletismografia/métodos , Pele/irrigação sanguínea , Adulto , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional/fisiologia , Adulto JovemRESUMO
The lactate threshold is used by athletes to optimise the intensity during exercise. It is of interest to measure the threshold on the very day and during the present sport activity. Steady state ergometer tests have been performed on 40 individuals to compare the threshold found by an electro acoustic sensor system to the lactate threshold established by blood analyses evaluated with the Dmax method. The correlation coefficient between the threshold found by the sensor system and the one established by blood analyses regarding workload (Watt), heart rate (beats/min), and lactate level (mmol lactate/l blood) at the thresholds were 0.87 (p < 0.001), 0.74 (p < 0.001), and 0.65 (p < 0.001), respectively. The findings in this study indicates that the thresholds of individuals measured by the sensor system show good correlations to the threshold established with the Dmax method from lactate levels in blood samples.
Assuntos
Limiar Anaeróbio/fisiologia , Testes Respiratórios/métodos , Ácido Láctico/sangue , Acústica , Adulto , Teste de Esforço/métodos , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Resistência Física/fisiologia , Carga de TrabalhoRESUMO
End tidal carbon dioxide measurements with an electro acoustic capnograph prototype have been demonstrated. The aim of this study was to verify that it is possible to obtain an adequate capnogram using the prototype and to investigate the influence of ambient temperature and humidity variations. By simultaneous measurements with a reference capnograph, on subjects performing exercise, hypo- and hyperventilation, P(ET)CO(2) readings from the reference were compared with the output signal from the prototype. The capnogram from the prototype correlated well with the reference in terms of breath time. The first parts of the expiration and inspiration phases were steeper for the reference than the prototype. The output signal from the prototype correlated well with the reference P(ET)CO(2) readings with a correlation coefficient of 0.93 at varied temperature and relative humidity.
Assuntos
Capnografia/instrumentação , Acústica/instrumentação , Testes Respiratórios/instrumentação , Desenho de Equipamento , Humanos , Umidade , TemperaturaRESUMO
The effects of low flow and reestablished normal flow on K+ balance and carboxylic acid balance was studied in perfused liver of 48-h starved rats at perfusate pH 7.4 and 6.8. The rate of net K+ release induced by ouabain was 1.8 mumol.min-1.g-1 at pH 7.4 and 1.4 mumol.min-1.g-1 at pH 6.8. Lowering of flow to 30% normal was accompanied by a transient, diphasic loss of K+ (max 0.15 mumol.min-1.g-1). Reestablished normal flow was immediately accompanied by a monophasic K+ uptake (max 0.35 mumol.min-1.g-1). These changes in potassium balance were independent of perfusate pH. Reduction of flow caused an almost immediate depolarization of 4 mV followed by a steady tendency to repolarization. Reestablished normal flow induced a transient hyperpolarization. Production of carboxylic acids during the low flow period did not correlate with the diphasic time course of K+ loss, and carboxylic acid uptake after reestablishment of flow did not correlate with the transient uptake of K+. The data show that the initial phase of K+ loss during low flow is due to inhibition of the Na(+)-K(+)-pump; the second phase may be reasonably explained by increased K+ permeability concomitant to cellular volume regulation.
Assuntos
Circulação Hepática , Fígado/metabolismo , Potássio/metabolismo , Animais , Ácidos Carboxílicos/metabolismo , Membrana Celular/fisiologia , Ácidos Graxos não Esterificados/farmacologia , Feminino , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Corpos Cetônicos/metabolismo , Cinética , Fígado/efeitos dos fármacos , Fígado/fisiologia , Potenciais da Membrana , Ouabaína/farmacologia , Consumo de Oxigênio/efeitos dos fármacos , Perfusão , Ratos , Ratos EndogâmicosRESUMO
1. The effects of ouabain on hepatic oxygen uptake, cell membrane potential, and Na-K transport were examined at 37 degrees C during non-recirculating perfusion of isolated livers from fasted normal rats and rats treated with triiodothyronine (T3). The perfusate was Krebs-Ringer bicarbonate buffer containing albumin and bovine erythrocytes. 2. Treatment with T3 increased the rate of hepatic oxygen uptake by 30% (i.e. by 0-83 (micromole/min) per gram liver). 3. After shifting to perfusate containing 2-5 mM ouabain, a 4-5 mV depolarization and maximal rates of net hepatic K release and Na uptake occurred within 2 min in both thyroid states. These changes were not accompanied by any significant change in the rates of hepatic oxygen uptake. 4. T3-treatment increased the maximal, post-ouabain net flux of K by 29% (i.e. by 0-52 (muequiv/min) per gram liver). The T3-indlced increase in the net flux of Na (19%) did not achieve statistical significance. 5. In either thyroid state, the observed passive fluxes of Na and K were calculated to be balanced by active vluxes at the expense of 5-6% of the observed rate of hepatic oxygen uptake. 6. The results indicate that hyperthyroidism may enhance the rate of hepatic Na-K transport, but the energy expenditure due to this process appears to be too small to make any important contribution to thyroid calorigenesis in perfused rat liver.
Assuntos
Regulação da Temperatura Corporal , Fígado/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Potássio/metabolismo , Sódio/metabolismo , Tri-Iodotironina/farmacologia , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Feminino , Potenciais da Membrana/efeitos dos fármacos , Ouabaína/farmacologia , RatosRESUMO
Changes in cell volume and 42K+ efflux associated with concentrative alanine uptake were studied in isolated rat hepatocytes suspended in Krebs-Ringer bicarbonate buffer. After addition of 10 mM-alanine, cellular water volume increased by 15% and the rate constant of 42K+ efflux by 250%. Alanine-induced 42K+ efflux was abolished by quinine and was strongly decreased when the cell-volume increase was counteracted by sucrose. The results suggest that K+ efflux during alanine uptake is implicated in a volume-regulatory response.
Assuntos
Alanina/metabolismo , Fígado/metabolismo , Potássio/metabolismo , Animais , Apamina/farmacologia , Água Corporal/metabolismo , Feminino , Furosemida/farmacologia , Técnicas In Vitro , Fígado/citologia , Fígado/efeitos dos fármacos , Quinina/farmacologia , Ratos , Ratos Endogâmicos , Sacarose/farmacologiaRESUMO
Na+-alanine cotransport across the cell membrane in isolated rat hepatocytes was studied. Changes in the cell membrane potential associated with the transport of alanine interfere with determination of the Na+-alanine coupling ratio of the cotransport. With valinomycin present to 'clamp' the cell membrane potential, a coupling ratio of 1:1 for the Na+-alanine influx was obtained.
Assuntos
Alanina/metabolismo , Fígado/metabolismo , Sódio/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Feminino , Técnicas In Vitro , Fígado/citologia , Fígado/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Valinomicina/farmacologiaRESUMO
The uptake of lactate, pyruvate and alanine in perfused rat liver was investigated under normal perfusion conditions (pH 7.4, PCO2 40 mmHg) and under conditions mimicking partially compensated metabolic acidosis (pH 6.9, PCO2 20 mmHg). At 1 mM lactate as well as 10 mM lactate in the medium a lowering of pH from 7.4 to 6.9 did not affect the lactate plus pyruvate uptake. A significant effect of the low pH was seen on pyruvate uptake which at 1 mM lactate was increased from 0.027 +/- 0.008(4) mumol/min per g liver at normal pH to 0.084 +/- 0.013(4) at low pH. At 10 mM lactate the liver produced pyruvate, but the production was significantly reduced by a lowering of the pH, being 0.45 +/- 0.13(8) mumol/min per g liver at pH 7.4 and 0.22 +/- 0.06(4) at pH 6.9. THe counterbalancing changes in lactate metabolism were too small to attain statistical significance. The stimulation of gluconeogenesis by an increase in FFA from 0 to 1 mM in the medium was unaffected by pH. Alanine uptake was decreased from 0.48 +/- 0.05(6) to 0.39 +/- 0.07(3) by lowering the pH from 7.4 to 6.9. We conclude that metabolic acidosis does not in itself inhibit the capacity of the perfused rat liver to remove lactate and pyruvate from the blood. If the same is true in man, no beneficial effect of bicarbonate treatment on lactate clearance in patients with lactic acidosis should be expected.
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Acidose/metabolismo , Alanina/metabolismo , Lactatos/metabolismo , Fígado/metabolismo , Animais , Glicemia/metabolismo , Feminino , Concentração de Íons de Hidrogênio , Ácido Láctico , Consumo de Oxigênio , Perfusão , Piruvatos/metabolismo , Ácido Pirúvico , Ratos , Ratos EndogâmicosRESUMO
The transport of alanine across the liver cell membrane was studied in hepatocytes isolated from fed and 48-h-fasted rats. Aminooxyacetate was used to render alanine nonmetabolizable. The steady-state intracellular-to-extracellular distribution ratio of alanine was maximal at extracellular concentrations below 0.5 mM and was increased from about 10 to about 20 by fasting. This increase was the net effect of a two- to threefold increase in the alanine influx and about a 50% increase in the rate constant of alanine efflux. The results suggest that alanine efflux occurred partly via the transport system mediating Na+-dependent alanine influx and partly by another pathway. The transmembrane Na+ electrochemical gradient remained unchanged by fasting and could apparently account for a maximal distribution ratio of alanine well above 20. In both nutritional states, the simplest kinetic model adequately describing the alanine influx implicated one saturable component besides a passive component. The apparent Vmax of the former was doubled by fasting while the apparent Km was insignificantly decreased. At low extracellular alanine concentrations, the rate of alanine consumption (aminooxyacetate absent) was only 40% of the alanine influx in the fed state but was increased at least fivefold by fasting and thereby balanced with the increased alanine influx. These results suggest a rate limitation at the transport level in the fasted state.
Assuntos
Alanina/metabolismo , Fígado/metabolismo , Ácido Amino-Oxiacético/farmacologia , Animais , Transporte Biológico , Membrana Celular/metabolismo , Jejum , Feminino , Técnicas In Vitro , Cinética , Ratos , Ratos Endogâmicos , Sódio/metabolismoRESUMO
End tidal carbon dioxide measurement with an electro-acoustic sensor is demonstrated. The sensor consists of an acoustic resonator coupled to a low cost electro-acoustic element. By simultaneous measurements with a reference sensor, the new device was tested on subjects performing exercise, hypo- and hyperventilation whereby the CO
RESUMO
Hepatic cell membrane potentials, hepatic cyclic adenosine 3',5'-monophosphate concentrations, and blood glucose levels were measured in anesthetized rats before, and at various times after, partial hepatectomy. In fed rats, hyperpolarization became evident 1-3 h postoperatively, reached its first peak at 4 h, and was maintained for approximately 36 h. The early phase of hyperpolarization was preceded by depletion of glycogen from the liver remnant and occurred during a decline of blood glucose concentrations below the level in sham-operated rats. Preoperative exhaustion of glycogen stores by fasting for 48 h resulted in marked hyperpolarization within 15 min after partial hepatectomy. In fasted rats, an intravenous injection of glucose (10 mmol X kg-1) caused a delay in hyperpolarization when given 30 min before partial hepatectomy, or a transient normalization of the membrane potentials when given 30 min after partial hepatectomy. Liver tissue cyclic adenosine 3',5'-monophosphate concentrations in fed rats remained largely unchanged 2 h after partial hepatectomy but increased greatly at 4 h. On the other hand, in fasted rats a significant increase was seen within 30 min. Glucose administration to fasted rats depressed cyclic adenosine 3',5'-monophosphate concentrations in the liver remnant. The results suggest that intensified gluconeogenesis, partly mediated by cyclic adenosine 3',5'-monophosphate, could be the event underlying early hepatocellular hyperpolarization induced by partial hepatectomy.
Assuntos
AMP Cíclico/metabolismo , Glucose/farmacologia , Hepatectomia , Fígado/metabolismo , Animais , Glicemia/metabolismo , Jejum , Feminino , Fígado/fisiologia , Glicogênio Hepático/metabolismo , Masculino , Potenciais da Membrana , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
Acid-base balance during development of diabetic ketoacidosis was reappraised on the basis of old studies on urinary excretion of ions. Circulatory collapse with impaired urinary excretion of acids is a prominent feature of the late phase of diabetic ketoacidosis, in which pathophysiological measurements are difficult to make. To elucidate the balance between hepatic uptake of carboxylic acids (free fatty acids and lactate plus pyruvate) and hepatic release of carboxylic acids (ketone bodies and lactate plus pyruvate) during the late phase of diabetic ketoacidosis, perfused livers from normal and streptozotocine-diabetic rats, fasted for 48 h, were subjected to high perfusate glucose concentrations, low perfusate pH and low perfusate flow rates. Provided that flow was kept normal, there was always a net uptake of carboxylic acids. At normal flow, a low pH and a high glucose concentration in the perfusate did not affect the hepatic uptake of lactate plus pyruvate or the flux of carbon from lactate to glucose. Reduction of the perfusate flow rate by two-thirds invariably turned the liver into a state of net carboxylic acid production. The net uptake of lactate plus pyruvate was greatly reduced, mainly due to initiation of a glycolytic flux.
Assuntos
Equilíbrio Ácido-Base , Cetoacidose Diabética/fisiopatologia , Animais , Glicemia/metabolismo , Creatina/urina , Ácidos Graxos não Esterificados/sangue , Feminino , Corpos Cetônicos/sangue , Rim/fisiopatologia , Glicogênio Hepático/metabolismo , Consumo de Oxigênio , Potássio/metabolismo , Ratos , Ratos EndogâmicosRESUMO
The pharmacokinetics of E. coli derived recombinant human interleukin-3 (rhIL-3) was studied following intravenous (i.v.) and subcutaneous (s.c.) bolus injection of rhIL-3. After i.v. bolus injection in eight patients, serum peak levels of 34.5-135.0 ng/ml were reached, followed by a rapid decline with a t1/2 alpha of 17 +/- 2 min and a t1/2 beta of 59 +/- 7 min. After s.c. bolus injection in five patients, the absorption was more prolonged with peak serum levels reached at 2.8 +/- 0.4 h. Elimination was also more protracted, and serum base-line levels were reached at 14-24 h. The immediate effect of rhIL-3 on peripheral white blood cells was less pronounced and more variable than previously found for G- or GM-CSF. Following i.v. administration, neutrophils showed a moderate drop to median 64% of initial values (range 42-85%) at median 30 min after injection (range 15-60 min) followed by an increase at 24 h to 69-288% of initial values. Eosinophils dropped to a median nadir of 34% and then gradually increased to maximum values in the range 135-720% at 18-24 h. The effect of rhIL-3 was further examined following i.v. injection of autologous 111Indium-labelled granulocytes in six patients. In steady state, i.v. injection of rhIL-3 caused a moderate drop in 111Indium activity of peripheral blood within 20 min without tendency to subsequent recovery. No change occurred in the activity recorded over the lungs and liver. The activity over the spleen decreased moderately in two patients. These results are strikingly different from those previously obtained after i.v. injection of rhGM-CSF.