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Biomedical subjects

N Klein

Publications and source records attributed to N Klein.

At least 19 recordsLinked to original sources
PubMed2006

In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram.

BACKGROUND: Escitalopram is a dual serotonin reuptake inhibitor (SSRI) approved for the treatment of depression and anxiety disorders. It is the S-enantiomer of citalopram, and is responsible for the serotonin reuptake activity, and thus for its pharmacological effects. Previous studies pointed out that clinically efficacious doses of other SSRIs produce an occupancy of the serotonin reuptake transporter (SERT) of about 80% or more. The novel radioligand [123I]ADAM and single photon emission computer tomography (SPECT) were used to measure midbrain SERT occupancies for different doses of escitalopram and citalopram. METHODS: Twenty-five healthy subjects received a single dose of escitalopram [5 mg (n=5), 10 mg (n=5), and 20 mg (n=5)] or citalopram [(10 mg (n=5) and 20 mg (n=5)]. Midbrain SERT binding was measured with [(123)I]ADAM and SPECT on two study days, once without study drug and once 6 h after single dose administration of the study drug. The ratio of midbrain-cerebellum/cerebellum was the outcome measure (V3") for specific binding to SERT in midbrain. Subsequently, SERT occupancy levels were calculated using the untreated baseline level for each subject. An Emax model was used to describe the relationship between S-citalopram concentrations and SERT occupancy values. Additionally, four subjects received placebo to determine test-retest variability. RESULTS: Single doses of 5, 10, or 20 mg escitalopram led to a mean SERT occupancy of 60+/-6, 64+/-6, and 75+/-5%, respectively. SERT occupancies for subjects treated with single doses of 10 and 20 mg citalopram were 65+/-10 and 70+/-6%, respectively. A statistically significant difference was found between SERT occupancies after application of 10 and 20 mg escitalopram, but not for 10 and 20 mg citalopram. There was no statistically significant difference between the SERT occupancies of either 10 mg citalopram or 10 mg escitalopram, or between 20 mg citalopram and 20 mg escitalopram. Emax was slightly higher after administration of citalopram (84%) than escitalopram (79%). In the test-retest study, a mean SERT "occupancy" of 4% was found after administration of placebo, the intraclass correlation coefficient was 0.92, and the repeatability coefficient was 0.25. CONCLUSION: SPECT and [123I]ADAM were used to investigate SERT occupancies after single doses of escitalopram or citalopram. The test-retest study revealed good reproducibility of SERT quantification. Similar SERT occupancies were found after administration of equal doses (in respect to mg) of escitalopram and citalopram, giving indirect evidence for a fractional blockade of SERT by the inactive R-citalopram.

Administration, Oral↗
PubMed2006

[Modern pacing therapy].

Since pacemakers first have been implanted in 1958 considerable technical progress has been achieved. The devices are more efficient today, have complex diagnostic functions, memory capacity and it is even possible to get telemetric software updates. Automatic mode switch due to changing heart rhythm, adaptation of AV-delay, auto sensing and auto stimulation threshold are available and facilitate pacemaker follow up. Because of continuously progress in pacing therapy guidelines have to be updated very often. The newest German and international guidelines for pacing therapy have been published in 2005 by Deutsche Gesellschaft für Kardiologie/ Herz- und Kreislaufforschung (DGK). Indications for pacing therapy increases continuously. Not only bradycardia, but also heart failure, prophylactic pacing to prevent and to terminate tachyarrhythmias are modern fields of pacing therapy.

Bradycardia↗
PubMed2006

Mannose-binding lectin in innate immunity: past, present and future.

The human collectin, mannose-binding lectin (MBL), is an important protein of the humoral innate immune system. With multiple carbohydrate-recognition domains, it is able to bind to sugar groups displayed on the surfaces of a wide range of microorganisms and thereby provide first-line defence. Importantly, it also activates the complement system through a distinctive third pathway, independent of both antibody and the C1 complex. Three single point mutations in exon 1 of the expressed human MBL-2 gene appear to impair the generation of functional oligomers. Such deficiencies of functional protein are common in certain populations, e.g. in sub-Saharan Africa, but virtually absent in others, e.g. indigenous Australians. MBL disease association studies have been a fruitful area of research and implicate a role for MBL in infective, inflammatory and autoimmune disease processes. Overall, there appears to be a genetic balance in which individuals generally benefit from high levels of the protein. However, in certain situations, reduced levels of circulating MBL may be beneficial to the host and this may explain the persistence of the deleterious gene polymorphisms in many population groups.

Complement C1↗
PubMed2005

Primary and immortalised human pancreatic islet endothelial cells: phenotypic and immunological characterisation.

AIMS/HYPOTHESIS: Studies on the biology of the microvascular endothelial cells (MECs) that surround and penetrate the pancreatic islets are hampered by difficulties in isolating and culturing large numbers of pure cells. We aimed to morphologically and functionally characterise primary MECs purified and cultured from human islets, and to establish a simian virus 40 (SV40)-immortalised cell line from these primary cultures. MATERIALS AND METHODS: Human islet MECs were extracted and purified using anti-CD105 coated immunomagnetic beads, and endothelial markers and surface molecules analysed by flow cytometric analysis. An immortalised cell line was then established by using a chimeric adeno5/SV40 virus. RESULTS: Islet MECs expressed classic and specific endothelial markers, a high basal level of intercellular adhesion molecule-1, and low levels of E-selectin and TNF (previously known as TNF-alpha) inducible vascular cell adhesion molecule-1. IFNG (previously known as IFN-gamma) induced expression of HLA class II molecules. The immortalised islet MECs expanded rapidly, exhibited increased DNA synthesis, and were passaged approximately 30 times, without signs of senescence. They retained the endothelial characteristics of the parental cells, and behaved as the primary cells in terms of TNF stimulation of expression of adhesion molecules and support of leucocyte adhesion and transmigration. CONCLUSIONS/INTERPRETATION: The immortalised islet MECs that we have established could effectively represent a substitute for primary counterparts for in vitro studies on the role of the microvasculature in pathophysiological processes involved in type 1 and type 2 diabetes.

Cell Adhesion↗
PubMed2005

Expression of nephrin by human pancreatic islet endothelial cells.

AIMS/HYPOTHESIS: The islet microcirculation has morphological characteristics resembling those of renal glomeruli. Transcription of the nephrin gene, a highly specific barrier protein of the slit diaphragm of podocyte foot processes, has been reported in the pancreas, although its cellular localisation and function remain to be defined. In this study, we purified and characterised microvascular endothelial cells (MECs) isolated from human islets and investigated the expression and distribution of nephrin on these cells. METHODS: Human islet MECs were extracted and purified using anti-CD105-coated immunomagnetic beads and their endothelial characteristics were confirmed by expression of classical endothelial markers and basal high-level expression of intercellular adhesion molecule-1 and TNF-alpha-inducible vascular cell adhesion molecule-1. Nephrin expression was assessed by immunofluorescence, flow cytometric analysis and western blotting on cell lysates, as well as by RT-PCR. RESULTS: Immunofluorescence studies detected nephrin in a fine, punctate, diffuse pattern on cultured islet MECs, and also in human pancreatic islet sections. In both cases nephrin colocalised with endothelial markers. TNF-alpha treatment induced a marked reduction and redistribution of the protein in one or multiple aggregates. Nephrin expression was confirmed by flow cytometry, western blotting and RT-PCR studies. In contrast, nephrin could not be detected at the protein or mRNA level in human macro- and microvascular cells from other sites. CONCLUSIONS/INTERPRETATION: Nephrin is expressed at protein and mRNA levels in islet microendothelium, supporting the hypothesis that islet MECs exhibit distinctive morphological characteristics that indicate functional specialisation of potential pathophysiological importance.

Cells, Cultured↗
PubMed2005

Access of HTB, main metabolite of triflusal, to cerebrospinal fluid in healthy volunteers.

OBJECTIVE: Triflusal has been shown to exert neuroprotective effects by downregulating molecules considered responsible for the development of Alzheimer's disease (AD). The aim of this study was to develop a population pharmacokinetic model to characterize plasma and cerebrospinal fluid (CSF) pharmacokinetics of the main active metabolite of triflusal-HTB (2-hydroxy-4-trifluoro-methylbenzoic acid)-in healthy volunteers. METHODS: Data from two studies were combined. Study A: subjects received single oral doses of triflusal 900 mg. Triflusal and HTB plasma concentrations were extensively measured. Study B: triflusal 600 mg once daily was administered orally for 14 days. HTB plasma and CSF concentrations were determined in healthy volunteers. Population pharmacokinetic modeling was performed using NONMEM. RESULTS: A one-compartmental model with rapid first-order absorption for triflusal and first-order formation of HTB best described plasma concentrations. Triflusal elimination rate constant was 50 times faster than that estimated for the metabolite. CSF concentrations of HTB ranged between 0.011 microg/ml and 0.341 microg/ml. A CSF-plasma partition coefficient of 0.002 and a k(e0) value of 0.059 h(-1) were estimated by means of population modeling. CONCLUSION: In the present study in healthy volunteers, HTB penetrated into the CSF in a range of concentrations experimentally proven to have protective effects in AD. These concentrations suggest that triflusal could be used in the treatment of central nervous system diseases in doses similar to those used in cardiovascular diseases. Access to the CSF compartment was characterized by a slow equilibrium rate constant and a low CSF-plasma partition coefficient.

Adult↗
PubMed2005

[Cardiac arrest caused by an ecstasy intoxication].

We report about a 19 years old man, suffering from an cardiac arrest (ventricular fibrillation) caused by an ecstasy intoxication. A supraventricular tachycardia was recorded on day three after resuscitation. No pathological findings were demonstrated by coronary angiography. An slow- fast- av -nodal- reentry- tachycardia (AVNRT) was detected and successfully treated by electrical ablation of the slow pathway during electrophysiological mapping. No severe neurological deficits were found in discharge from hospital.

Adult↗
PubMed2005

Effect of exercise on transdermal nicotine release in healthy habitual smokers.

OBJECTIVE: Transdermal nicotine patches have become a frequently prescribed tool in smoking cessation programs during the past years. However, there is circumstantial evidence that transdermal nicotine release substantially varies with physical activity producing toxic plasma concentrations that may account for severe adverse events. METHODS: We, therefore, compared nicotine release from two different transdermal nicotine systems (TDNS) at rest and during strenuous physical activity in a two-period crossover study in healthy smokers (n = 10). The subjects were randomly assigned to receive either 21 mg/day of formulation A or B on study Day 1 and 2. Patches were applied eight hours before starting standardized physical activity, and nicotine concentrations were measured in plasma and topically in the tissue layers underneath the application site by microdialysis. RESULTS: There was no difference between groups in the mean values for area under the time-concentration curve at rest from 0 - 8 hours AUC(0-8) (p < 0.799) and during exercise from 8 - 11 hours AUC(8-11) (p < 0.878). C(max) values between groups with C(max) values of 16.4 +/- 9.5 ng/ml and 16.0 +/- 10.7 ng/ml at rest (p < 0.919, NS) and 10.05 +/- 6.8 ng/ml and 10.2 +/- 6.9 ng/ml (p < 0.959, NS) during exercise did not differ significantly. Nicotine tissue concentrations increased two-fold during exercise versus baseline (p < 0.878). Skin blood flow increased significantly during exercise compared with baseline (p < 0.001). No adverse events were observed. CONCLUSION: The present study provides evidence that transdermal nicotine release from TDNS increases during exercise. However, this increase has no significant effect on overall plasma pharmacokinetics. Our pharmacokinetic data further indicate that the two TDNS formulations are equivalent during conditions of rest and exercise.

Administration, Cutaneous↗
PubMed2004

Vbeta-restricted T cell adherence to endothelial cells: a mechanism for superantigen-dependent vascular injury.

OBJECTIVE: To investigate the potential for endothelial cells to operate as superantigen-presenting cells for T cells and the potential for such an interaction to cause endothelial cell activation and injury. METHODS: Class II major histocompatibility complex (MHC)-positive human umbilical vein endothelial cells (HUVECs) were cocultured for 4 hours with purified T cells and the superantigens staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin 1 (TSST-1). After staining with fluorescence-conjugated monoclonal antibodies, flow cytometric analysis was performed on the HUVECs and T cells to examine V(beta)-restricted T cell adherence to the endothelial cell monolayer, V(beta)-restricted T cell activation (CD69 up-regulation), surface expression of endothelial cell activation markers, and generation of endothelial microparticles (EMPs). RESULTS: Coculture of purified T cells with class II MHC-positive HUVECs and either TSST-1 or SEB resulted in V(beta)-restricted CD69 up-regulation by CD4 and CD8 cells (V(beta)2 activation for TSST-1; V(beta)3, V(beta)5.1, and V(beta)12 activation for SEB). Additionally, there was CD4 and CD8 T cell V(beta)-restricted adherence to the HUVEC monolayer at 4 hours. Expression of intercellular adhesion molecule 1, E-selectin, and vascular cell adhesion molecule 1 was up-regulated on the class II MHC-positive HUVECs following exposure to superantigen in the presence of T cells, and there was increased EMP release from activated HUVECs, which occurred earlier and was of greater magnitude than that observed in response to tumor necrosis factor alpha. CONCLUSION: Class II MHC-positive endothelial cells operate as competent superantigen-presenting cells for CD4 and CD8 lymphocytes in vitro. Dual signaling between endothelial cells and T cells results in V(beta)-restricted activation and adherence to endothelial monolayers and endothelial cell activation and release of EMPs expressing inducible cell adhesion molecules. It is proposed that this mechanism could account in part for the vascular injury associated with superantigen-mediated diseases including Kawasaki disease.

Antigen-Presenting Cells↗
PubMed2004

Endothelial and platelet microparticles in vasculitis of the young.

OBJECTIVE: Microparticles are released from endothelial cells in response to a variety of injurious stimuli and recently have been shown to be increased in a number of diseases associated with endothelial dysfunction. This study examined endothelial microparticle (EMP) and platelet microparticle (PMP) profiles in children with systemic vasculitis to test the hypothesis that EMPs may provide a noninvasive means of examining endothelial activation or injury. METHODS: The study cohort comprised 39 children with systemic vasculitis at various stages of disease activity, 24 control children with febrile disease, and a control group of 43 healthy subjects. Plasma was ultracentrifuged at 17,000g for 60 minutes, and the microparticle pellets were examined using flow cytometry. RESULTS: Plasma from patients with active systemic vasculitis contained significantly higher numbers of E-selectin-positive EMPs compared with that from patients in remission, healthy controls, or febrile disease controls (P = 0.000 for each). A similar result was obtained for the numbers of EMPs expressing the marker CD105. There was also a significant increase in PMPs expressing CD42a in the active vasculitis group as compared with the other groups, but this difference was not significant for PMPs expressing P-selectin. The EMP counts correlated with the Birmingham Vasculitis Activity Score and the acute-phase reactant levels in the patients with systemic vasculitis, but there was a poor correlation overall between EMP counts and the acute-phase reactant levels in the febrile disease controls. CONCLUSION: EMPs may provide a window to the activated endothelium and could provide important pathophysiologic insights into the vascular injury associated with vasculitis of the young.

Acute-Phase Proteins↗
PubMed2004

Impaired pulmonary status in cystic fibrosis adults with two mutated MBL-2 alleles.

Mannose-binding lectin has recently been identified as a modifier of severity in cystic fibrosis, although studies have produced differing results and the mechanism of action remains unclear. The current authors have studied large cohorts of adults (n=298) and children (n=260) to explore this apparent relationship further. Adults with two structural mutations, but not heterozygotes, had significantly reduced lung function and oxygen saturations, more frequent hospital admissions and raised systemic inflammatory markers. This was not related to increased rates of infection with Pseudomonas aeruginosa, and there was no increased susceptibility to Burkholderia cepacia. None of these findings was mirrored in the paediatric cohort. In conclusion, severe mannose-binding lectin deficiency appears to be detrimental to cystic fibrosis adults, although heterozygotes are not affected. It is suggested that this is not related to impaired complement-mediated bacterial killing, and a link with the host inflammatory response is hypothesised. If mannose-binding lectin replacement is developed as a new approach to treatment for this disease, the present study would suggest that the small group of severely deficient patients with two structural mutations may be the group to benefit.

Adult↗
PubMed2004

Circulating aldosterone levels are unexpectedly low in children with acute meningococcal disease.

The incidence of meningococcal disease in childhood has risen over the past decade. Mortality remains high for those who develop septic shock and purpura fulminans. Poor perfusion, hypotension, and loss of intravascular circulating volume may be expected to influence both mineralocorticoid and glucocorticoid secretion. The aim of the study was to define adrenocortical hormone status at presentation. Sixty children admitted to the pediatric intensive care unit were studied. Children were divided into two groups: group A (n = 31), with meningococcal sepsis, mean age 4.4 yr (range 0.5-14.4), predicted risk of mortality mean 32.3% (range 0.5-99.3%); and group B (n = 29), with other diagnoses (post major surgery and with severe respiratory infections), mean age 4.1 yr (range 0.3-16.3), predicted risk of mortality mean 9.4% (range 0.2-83%). The groups were not significantly different for age. Plasma levels of aldosterone and cortisol were determined by RIA. The mean plasma aldosterone concentration on admission in group A was 427.5 +/- 88.1 pg/ml, with 96.7% of values within the normal range for age for healthy children and were significantly lower than group B mean, 1489.2 +/- 244.2 pg/ml (P < 0.0001), with 59.3% of values above the normal range. In group A there was no correlation with plasma concentrations of sodium, potassium, or volume of colloid infused in the previous 8 h. In group A mean serum cortisol mean values were 799.5 +/- 75.9 nmol/liter and in group B cortisol levels were 703.4 +/- 78.6 nmol/liter (P = n.s.). We conclude that children with meningococcal disease present with lower plasma aldosterone concentrations than other patients in the pediatric intensive care unit, for which there is no clear explanation. Further work is needed to elucidate the mechanisms underlying this finding and to examine its clinical implications.

Acute Disease↗
PubMed2003

Anomalous coherence peak in the microwave conductivity of c-axis oriented MgB2 thin films.

The temperature dependence of the real part of the microwave complex conductivity at 17.9 GHz obtained from surface impedance measurements of two c-axis oriented MgB2 thin films reveals a pronounced maximum at a temperature around 0.6 times the critical temperature. Calculations in the frame of a two-band model based on Bardeen-Cooper-Schrieffer (BCS) theory suggest that this maximum corresponds to an anomalous coherence peak resembling the two-gap nature of MgB2. Our model assumes there is no interband impurity scattering and a weak interband pairing interaction, as suggested by band structure calculations. In addition, the observation of a coherence peak indicates that the pi band is in the dirty limit and dominates the total conductivity of our films.

Journal Article↗
PubMed2003

Value of negative spiral CT angiography in patients with suspected acute PE: analysis of PE occurrence and outcome.

The aim of this study was to analyze pulmonary embolism (PE) occurrence and retrospective clinical outcome in patients with clinically suspected acute PE and a negative spiral CT angiography (SCTA) of the pulmonary arteries. Within a 35-month period, 485 consecutive patients with clinical symptoms of acute PE underwent SCTA of the pulmonary arteries. Patients with a negative SCTA and without anticoagulation treatment were followed-up and formed the study group. Patient outcome and recurrence of PE was evaluated retrospectively during a period of 6 months after the initial SCTA, and included a review of computerized patient records, and interviews with physicians and patients. Patients were asked to fill out a questionnaire concerning all relevant questions about their medical history and clinical course during the follow-up period. Special attention was focused on symptoms indicating recurrent PE, as well as later confirmation and therapy of PE. Of the 485 patients, 325 patients (67%) had a negative scan, 134 (27.6%) had radiological signs of PE, and 26 (5.4%) had an indeterminant result. Of 325 patients with a negative scan, 269 (83%) were available for follow-up. The main reasons for loss to follow-up were change of address, name, or phone number, or non-resident patients who left abroad. Of 269 patients available for follow-up, 49 patients (18.2% of 269) received anticoagulant treatment because of prior or recent deep venous thrombosis (32.6%) or a history of PE (34.7%), cardiovascular disease (18.4%), high clinical probability (8.2%), positive ventilation-perfusion scan (4.2%), and elevated D-dimer test (2%). The remaining 220 patients, who did not receive anticoagulant medication, formed the study group. Of this study group, 1 patient died from myocardial infarction 6 weeks after the initial SCTA, and the postmortem examination also detected multiple peripheral emboli in both lungs ( p=0.45%; 0.01-2.5, 95% confidence interval). The PE did not occur in any other patient. In patients with suspected PE and negative SCTA without anticoagulant therapy, the risk of recurrent PE in this study was less than 1% and similar to that in patients after a negative pulmonary angiogram. Therefore, we conclude that patients can be managed safely without anticoagulation therapy; however, this approach may not be appropriate for critically ill patients and those with persistent high clinical suspicion of acute PE.

Adolescent↗
PubMed2003

Growth hormone enhances proinflammatory cytokine production by monocytes in whole blood.

Growth hormone (GH) has been used as anabolic therapy to treat catabolic patients. In a recent study, however, administration of high doses of GH to critically ill adults was associated with an increase in morbidity and mortality. Preponderance of septic shock and uncontrolled infections as causes of death in these patients suggests an immuno-modulatory effect of GH. Our hypothesis was that GH treatment may modulate the production of proinflammatory cytokines, which are implicated in sepsis. In our study, human monocytes in whole blood were activated with lipopolysaccaharide (LPS) (1-100 ng/ml) purified from a clinical isolate of group B Neisseria meningitidis in the presence of a high dose of GH (100 ng/ml). The subsequent proinflammatory cytokine response was analysed by intracellular cytokine staining and flow cytometry. Our results show that GH enhances IL1-alpha, IL-6 and TNF-alpha production by LPS activated monocytes in whole blood. The modulation of cytokines by GH may be responsible for the adverse consequences of GH in critically ill patients.

Adult↗
PubMed2003

T cell Vbeta repertoires in childhood vasculitides.

Superantigens (SAgs) are potent stimulators of T cells bearing specific Vbeta T cell receptors (TCR) and may play a role in the aetiopathogenesis of systemic vasculitis, although this remains contentious. To investigate the possible aetiological role of SAgs, this study examined peripheral blood T cell Vbeta repertoires in children with systemic vasculitis. FACS analysis of 17 different peripheral blood T cell Vbeta families was performed in 20 healthy control children, 27 disease control children with nonvasculitic inflammatory disease, 25 children with primary systemic vasculitis, six patients with Kawasaki disease (KD) and six patients with Henoch-Schönlein purpura (HSP). There was a significantly increased variance of CD4 Vbeta12 and Vbeta17, and CD8 Vbeta1 in the primary systemic vasculitis group compared to control and disease controls. Moreover, 80% of the primary systemic vasculitis children had one or more CD4 Vbeta expansions or deletions, compared with 30% of controls (P < 0.002), and 37% of the disease controls (P < 0.002). In the KD group, the mean percentage of CD4 Vbeta2 T cells was higher than in controls or disease controls. In the HSP group, there was no consistent skewing of the T cell Vbeta repertoire. We have observed changes in the T cell Vbeta repertoire in children with vasculitis over and above those observed in disease controls. While these data provide impetus for further research into this contentious field, they do not resolve unequivocally the question of the role of SAgs in childhood vasculitic syndromes.

Adolescent↗
PubMed2003

Transcapillary insulin transfer in human skeletal muscle.

BACKGROUND: Transcapillary insulin transfer is considered a rate-limiting step in insulin action at supraphysiological insulin concentrations. However, it remains unclear whether this concept also applies for physiological conditions. MATERIALS AND METHODS: In the present study we set out to characterize transcapillary insulin transfer by measuring insulin concentrations in plasma and interstitial space fluid of skeletal muscle during an oral glucose tolerance test and euglycaemic hyperinsulinaemic clamp conditions, respectively. For this purpose we employed in vivo microdialysis of skeletal muscle in conjunction with an ultrasensitive insulin assay in eight healthy lean male volunteers (aged 25 +/- 1 years). RESULTS: Insulin concentrations at baseline were 48 +/- 8 pmol x L(-1) in plasma and 19 +/- 4 pmol x L(-1) in the interstitium (P = 0.002). The mean interstitium to plasma ratio at baseline was 0.48 +/- 0.09 pmol x L(-1). During the oral glucose tolerance test the interstitium to plasma ratio remained unchanged (0.43 +/- 0.12, P = NS vs. baseline), but was significantly reduced during euglycaemic hyperinsulinaemic clamp conditions at steady-state hyperinsulinaemia (0.12 +/- 0.01, P = 0.01 vs. baseline). CONCLUSION: In summary there is a substantial transcapillary insulin gradient in healthy human skeletal muscle under baseline and glucose-stimulated conditions. Our findings support the hypothesis of a saturable transcapillary insulin transport representing a partly rate-limiting step for insulin action.

Adult↗