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Biomedical subjects

A Asberg

Publications and source records attributed to A Asberg.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of the pharmacokinetic interaction between fluvastatin XL and cyclosporine in renal transplant recipients.

OBJECTIVE: To assess the pharmacokinetic interaction between cyclosporine and extended-release fluvastatin (fluvastatin XL), 80 mg for 7 days, in stable renal transplant recipients. METHODS: This was a single-center, open-label study. 17 renal transplant recipients received their standard cyclosporine therapy (Days 1 - 9) plus a once-daily single oral dose of fluvastatin XL, 80 mg (Days 2 - 8). Blood samples were collected and cyclosporine (whole blood) and fluvastatin (plasma) concentrations determined by radioimmunoassay and HPLC fluorescence detection, respectively. Pharmacokinetic parameters were calculated using non-compartment analysis and fluvastatin results were compared with historical controls. RESULTS: Treatment with fluvastatin XL, 80 mg for 7 days, had no significant effect on either the AUC0-12 (3,644 ng x h/ml in the absence of fluvastatin vs. 3,534 ng x h/ml in the presence of fluvastatin) or the Cmax of cyclosporine (983 ng/ml in the absence of fluvastatin vs. 945 ng/ml in the presence of fluvastatin). Co-administration of fluvastatin XL also had no effect on the tmax, t1/2 or apparent clearance (CL/F) of cyclosporine in renal transplant patients. The AUC and Cmax for fluvastatin XL in the presence of cyclosporine (AUC0-24 1,192 ng. x h/ml, Cmax 271 ng/ml) were approximately 2-fold higher compared with historical data for fluvastatin XL alone in healthy volunteers (AUC0-24 630 ng x h/ml, Cmax 102 ng/ml) but lower than the historical data for fluvastatin IR, 40 mg b.i.d. alone in healthy volunteers (AUC0-24 1,340 ng x h/ml, Cmax 443 ng/ml). Tmax, t1/2 and trough levels of fluvastatin in the presence of cyclosporine were also similar to the historical controls. Concomitant administration of cyclosporine and fluvastatin XL was well tolerated by renal transplant recipients. CONCLUSIONS: Fluvastatin XL, 80 mg, and cyclosporine do not show clinically relevant pharmacokinetic interactions.

Administration, Oral↗
PubMed2005

Iron status among 3005 women aged 20-55 years in Central Norway: the Nord-Trøndelag Health Study (the HUNT study).

OBJECTIVE: To describe the iron status of Norwegian women of fertile age, to show the prevalence of iron-deficiency anemia and iron overload, and to demonstrate possible factors connected to and/or influencing iron status. MATERIAL AND METHODS: The diagnostic criteria were: (a) anemia: hemoglobin (Hb) < 120, < 117, or < 115 g/l; (b) depleted iron stores: serum ferritin (SF) < 10 or 12 microg/l; iron-deficiency anemia: (a)+(b). Iron overload: SF > or = 110 microg/l. The study was conducted in Central Norway where a total of 3005 women aged 20 to 55 years were enrolled in a health survey program (the HUNT Study). None of the women were pregnant and none had been blood donors in the two previous years. RESULTS: Median SF was 31.0 microg/l. Depleted iron stores were present in 10.9 and 15.1%, respectively. The Hb 2.5%tile among the iron-replete women was 117 g/l. With this cut-off value, anemia was present in 4.7% and iron-deficiency anemia in about 3%. Iron overload was present among 5.2%, and homozygous primary hemochromatosis among 0.4%. CONCLUSIONS: The prevalence of iron-deficiency anemia was relatively low and similar to that found earlier in small groups of Norwegian women. The prevalence is comparable with results from other developed countries.

Adult↗
PubMed2005

Effects of autotransfusion of mediastinal shed blood on biochemical markers of myocardial damage in coronary surgery.

BACKGROUND: Previous studies have shown conflicting results regarding the effect of autotransfusion of mediastinal shed blood after coronary artery bypass grafting (CABG) on the serum levels of myocardial band (MB) isoenzymes of creatine kinase (CK-MB) and cardiac troponins. The effect of autotransfusion on serum levels of human heart fatty acid binding protein (H-FABP), another marker of myocardial necrosis, has not been studied. The aim of the present study was to investigate the effects of autotransfusion of mediastinal shed blood on the serum levels of CK-MB, cardiac troponin T (cTnT), and H-FABP after uncomplicated primary CABG. METHODS: Fifty patients were randomized to post-operative autotransfusion of mediastinal shed blood or no autotransfusion. Blood samples for the analysis of the biochemical markers of myocardial damage were drawn pre-operatively and 1, 4, 12, 24, 48, and 72 h after the termination of cardiopulmonary bypass. Samples from the mediastinal shed blood were collected after 1 and 4 h. RESULTS: The levels of the biochemical markers of myocardial injury were all markedly elevated in mediastinal shed blood. Autotransfusion did not significantly affect the serum levels of cTnT or H-FABP. However, during the early post-operative hours, there was a trend towards a higher level of cTnT and H-FABP in the autotransfusion group. During the first 24 h after surgery, the autotransfusion group had a significantly higher serum level of CK-MB. CONCLUSION: Post-operative autotransfusion of mediastinal shed blood may contribute to elevated serum levels of biochemical markers of myocardial injury.

Aged↗
PubMed2005

Combined therapy with atorvastatin and calcineurin inhibitors: no interactions with tacrolimus.

Increased systemic exposure to statins and consequent risk for complications has been reported in patients concomitantly treated with cyclosporin A (CsA). This has been ascribed to inhibition of drug catabolism by cytochrome P450 3A4 (CYP3A4) or drug transport by P-glycoprotein (PGP) and organic anion transporting polypeptide (OATP1B1). It is not known whether the combination of statins and tacrolimus (Tac) also suffers from this drawback. Therefore, a pharmacokinetic study of atorvastatin and its metabolites was performed in 13 healthy volunteers after 4 days' treatment, and after short (12 h) concomitant exposure to CsA and Tac. A complementary assessment of overall CYP, and hepatic and intestinal CYP3A4+PGP activity was performed after each treatment episode and compared to baseline (no drugs). Systemic exposure to atorvastatin acid and its metabolites was significantly increased when administered with CsA. In contrast, intake of Tac did not have any impact on atorvastatin pharmacokinetics. Concomitantly, a profound decrease of hepatic and intestinal PGP and an increase of intestinal CYP3A4 were noted with CsA, whereas no effect was seen after atorvastatin therapy with or without Tac. Based on these findings treatment with Tac appears a safer option for patients needing a combination of statins and calcineurin inhibitors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Analytical quality goals derived from the total deviation from patients' homeostatic set points, with a margin for analytical errors.

The deviation of test results from patients' homeostatic set points in steady-state conditions may complicate interpretation of the results and the comparison of results with clinical decision limits. In this study the total deviation from the homeostatic set point is defined as the maximum absolute deviation for 95% of measurements, and we present analytical quality requirements that prevent analytical error from increasing this deviation to more than about 12% above the value caused by biology alone. These quality requirements are: 1) The stable systematic error should be approximately 0, and 2) a systematic error that will be detected by the control program with 90% probability, should not be larger than half the value of the combined analytical and intra-individual standard deviation. As a result, when the most common control rules are used, the analytical standard deviation may be up to 0.15 times the intra-individual standard deviation. Analytical improvements beyond these requirements have little impact on the interpretability of measurement results.

Clinical Chemistry Tests↗
PubMed2004

Headache prevalence related to haemoglobin and ferritin. The HUNT Study.

As clinic-based studies show an association between headache and both high and low levels of haemoglobin, we analysed this relationship in a population-based cross-sectional study (the HUNT Study). A total of 2385 women aged 20-55 years responded to a headache questionnaire and gave blood samples for measuring haemoglobin and ferritin. In the multivariate analyses, adjusting for age and education, there was a linear trend of decreasing prevalence of headache (P = 0.02) and migraine (P = 0.01) with decreasing haemoglobin. In particular, migraine was less likely among women with low haemoglobin (values < 11.5 g/dl) (odds ratio 0.4, confidence interval 0.2, 0.9). There was no correlation between headache prevalence and ferritin. The present findings may be relevant for the headache reported in polycythaemia and chronic altitude sickness.

Adult↗
PubMed2002

Reference intervals for procalcitonin and C-reactive protein after major abdominal surgery.

Procalcitonin (PCT). a new marker proposed as a diagnostic tool for bacterial infections, triggers a systemic-inflammatory reaction in the body (sepsis, septic shock) and has potential use in a wide range of patient settings. To interpret the results from PCT measurements, we depend on reference intervals established from relevant populations. PCT and C-reactive protein (CRP) concentrations were analysed in 47 patients with a normal postoperative course after major abdominal surgery. The mean concentration of PCT declines from the first day and reaches half its initial values on the second day after the operation. whereas the mean concentration of CRP increases in the first 48 h and reaches half its maximum value on the fifth day after the operation. We present a continuous reference interval for plasma PCT and CRP concentrations in the first week following major abdominal surgery. For PCT we also present a graphic display of expected mean and expected upper reference limits predicted from the value measured on the first postoperative day.

Abdomen↗
PubMed2002

Persons with screening-detected haemochromatosis: as healthy as the general population?

BACKGROUND: Hereditary haemochromatosis (HH) is a common genetic disease leading to iron deposition in the liver and other organs. Early treatment will prevent clinical disease and population-based screening for HH has been advocated. However, the benefit of screening depends on the morbidity of HH. We have compared the morbidity in HH persons detected by screening with the morbidity in the rest of the population. METHODS: All inhabitants 20 years or older in a Norwegian county (94,191 persons) were invited to participate in a health survey programme. Of 65,717 participating persons, a blood specimen for transferrin saturation was obtained from 65,238. After repeated laboratory testing and clinical examination, 269 persons were found to have phenotypic HH, while 297 had genotypic HH (the C282/C282Y mutation). Using self-reported data, clinical examinations and analysis of non-fasting blood samples, the morbidity in phenotypic and genotypic HH persons was compared with the morbidity in the rest of the population. All data were collected before subjects were diagnosed with HH, and all comparisons were corrected for age and gender. RESULTS: Compared to control persons, phenotypic and genotypic HH men and women had a higher score on 1 of 17 questions dealing with joint complaints. Phenotypic and genotypic HH women below 50 years of age had a higher prevalence of hypothyroidism (15.2% and 12.5%, respectively, compared to 3.0% in the control population). Phenotypic HH women below 50 years of age had higher diastolic blood pressure than control women. Phenotypic HH men above 50 years of age and genotypic HH men scored lower than control men on a compound myocardial infarction risk score variable, in part due to lower serum cholesterol concentration. Fewer phenotypic HH men above 50 years of age reported having angina pectoris. Otherwise, the health of phenotypic and genotypic HH persons was not different from the health of control persons. CONCLUSION: When corrected for age and gender, the morbidity in persons with screening-detected HH was not very different from the morbidity in the control group, indicating that population-based screening may not be as beneficial as anticipated.

Adult↗
PubMed2002

Benefit of population-based screening for phenotypic hemochromatosis in young men.

BACKGROUND: Hereditary hemochromatosis (HH) is a common genetic disease leading to accumulation of iron in the body, most notably in the liver. More men than women become clinically ill. The prognosis is excellent if phlebotomy treatment is started before liver cirrhosis develops. Screening has been recommended, but the benefit of population-based screening has never been shown in a randomized clinical trial. In this article, we estimate the benefit of screening young men, using a theoretical model. METHODS: A phenotypic screening scenario was modelled using a decision tree. Gain of quality-adjusted life-years was used as a measure of benefit, and estimated using Markov processes. Data on the accuracy of the screening tests, the prevalence of HH and the risk of liver cirrhosis were mainly derived from a cross-sectional study on the prevalence and morbidity of HH in 30509 men. Data on the excess mortality of cirrhosis were taken from relevant literature. Sensitivity analysis was done for important variables. RESULTS: Assuming basal case values for variables, screening a cohort of 1000 men aged 30 years for phenotypic HH would gain about 8 quality-adjusted life-years, compared to awaiting symptomatic disease. Based on actual costs of our cross-sectional study, the screening cost was US$250 per quality-adjusted life-year gained. The prevalence of phenotypic HH, the excess mortality of liver cirrhosis, the quality of life in non-cirrhotic HH patients, and the fractions of patients compliant with treatment were the most important variables in the sensitivity analysis. CONCLUSION: Incorporating screening for phenotypic HH in health survey programmes for young men may be worthwhile.

Adult↗
PubMed2002

Intake of grapefruit juice alters the metabolic pattern of cyclosporin A in renal transplant recipients.

OBJECTIVE: The aim of the present study was to investigate the effect of grapefruit juice on the pharmacokinetics of cyclosporin A (CsA), as Sandimmun Neoral, and its main metabolites, M1, M9 and M4N, in renal transplant recipients. METHODS: Ten renal transplant recipients, on CsA-based immunosuppressive therapy, were included in this open, randomized crossover study. Patients were given their individualized morning dose of CsA, administered with either 250 ml water or 250 ml grapefruit juice and 12-hour CsA pharmacokinetic investigations were performed. The 2 investigation days were separated by at least 7 days. RESULTS: Administration of CsA with grapefruit juice compared with water significantly increased the area under the whole blood concentration versus time curve in the interval from 0-12 hours (AUC(0-12)) of CsA, by an average of 25 +/- 19% (p = 0.002). Intake of grapefruit juice did not have any significant influence on maximum whole blood concentration (Cmax) or time to Cmax (tmax) of CsA. AUC(0-12) and Cmax of M9 decreased significantly with intake of grapefruit juice, on average 22 +/- 11% (p = 0.0007) and 36 +/- 6% (p = 0.0001), respectively. AUC(0-12) of M1, however, was on average 13 +/- 14% (p = 0.02) higher upon co-administration of CsA with grapefruit juice as compared with water. The level of M4N was below the limit of quantification in most samples, and an effect of co-administration of CsA with grapefruit juice could not be determined for this metabolite. CONCLUSION: The present study shows that co-administration of grapefruit juice with CsA compared with water affects the formation and/or elimination of the 2 metabolites M1 and M9 differently. In addition, administration of CsA with grapefruit juice compared with water induced a moderate, but significant increase in systemic exposure of CsA in renal transplant recipients.

Adolescent↗
PubMed2001

[Acute dialysis-dependent renal failure at the Rikshospital in 1998].

BACKGROUND: There are few epidemiological studies on acute renal failure, and as far as we know none have previously been conducted in Norway. The objective of this study was to evaluate the scope, etiology, treatment and results of dialysis-dependent acute renal failure based on data from the Norwegian National Hospital in 1998. MATERIAL: This study is based on data from a questionnaire applied to all patients (n = 44) treated with dialysis for acute renal failure at the Norwegian National Hospital in 1998. The questionnaire was designed by a group of Norwegian nephrologists in cooperation with the Norwegian Society of Nephrology. RESULTS: The incidence of dialysis-dependent acute renal failure was 54.4 per million population. Men constituted 75% of the patient population. The most common underlying disorders were heart disease, peripheral vascular disease, and cancer. 90% of patients had oliguric acute renal failure, most frequently due to postoperative complications, septicaemia or drugs, and in most cases the aetiology was multifactorial. Patients received on average nine intermittent hemodialysis treatments and stayed on average ten days in the intensive care unit. 30% of the patients were either heart, lung, liver or bone marrow transplanted (renal transplant patients were excluded). The 60 day mortality rate was 41%. INTERPRETATION: The incidence of dialysis-dependent acute renal failure was relatively high in the Norwegian National Hospital patient pool, combined with a significant mortality rate. These findings are comparable with those of other studies.

Acute Kidney Injury↗
PubMed2001

[Metabolic interactions with statins].

BACKGROUND: Isoenzymes of the cytochrome P450 (CYP) system play a prominent role in drug metabolism, including the HMG-CoA reductase inhibitors (statins). Alteration in metabolic activity is often the underlying mechanism of clinically relevant interactions, thus it is important to make a rational assessment of the risk for metabolic interactions with statins. MATERIAL AND METHODS: Articles covering the field of statin metabolism and related interactions were mainly searched for via PubMed. RESULT: More than 50% of the overall CYP metabolism is mediated through the isoenzyme CYP3A4, which is the main elimination route of simvastatin, lovastatin and atorvastatin. Interaction studies reveal that simvastatin and lovastatin have the highest potential for clinically relevant interactions related to this isoenzyme, most often leading to increased efficacy/toxicity of the statin. Interactions with agents that alter the activity of CYP3A4 can also be expected for atorvastatin. Other statins are to a lesser extent dependent on CYP3A4 in their elimination. Thus, pravastatin, cerivastatin and fluvastatin have a minor potential for interactions linked to this isoenzyme. Interactions associated with CYP2C9-interference may, however, be present for fluvastatin. INTERPRETATION: Since lipid-lowering therapy most often is life-long, the use of statins will frequently be accompanied by the use of multiple drugs, hence the importance of considering the risk for interactions when selecting statins.

Anti-Bacterial Agents↗
PubMed2001

Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients.

Atorvastatin is increasingly used as a cholesterol-lowering agent in solid organ transplant recipients receiving cyclosporine A (CsA). However, the potential bilateral pharmacokinetic interaction between atorvastatin and CsA in renal transplant recipients has not previously been examined. Baseline 12-h CsA pharmacokinetic investigation was performed in 21 renal transplant recipients and repeated after 4 weeks of atorvastatin treatment (10 mg/ d). At week 4, 24-h pharmacokinetics of atorvastatin was also performed. All patients received basiliximab induction followed by CsA and prednisolone immunosuppression. Compared with historic controls, CsA-treated patients showed, on average, sixfold higher plasma HMG-CoA reductase inhibitory activity after 4 weeks of atorvastatin treatment (p < 0.05). Atorvastatin had a moderate effect on the pharmacokinetics of CsA and reduced the AUC0-12 (area under curve, 0-12h) by 9.5 +/- 18% (p = 0.013) and Cmax (maximal concentration) by 13.5 +/- 24% (p =0.009), while C12 (trough level) was unchanged (p =0.42). Total and LDL cholesterol decreased by 26.8 +/- 8.4% (p < 0.0001) and 41.5 +/- 11.0% (p < 0.0001), respectively. Bilateral pharmacokinetic interaction between atorvastatin and CsA resulted in sixfold higher plasma HMG-CoA reductase inhibitory activity, but only a moderate decrease in systemic exposure of CsA.

Adult↗
PubMed2001

Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons.

BACKGROUND: Hereditary hemochromatosis (HH) is a common genetic disease leading to accumulation of iron in several organs, most notably the liver. The C282Y/C282Y mutation in the HFE gene is found in most cases. In order to prevent clinical disease and to study the cost and feasibility of screening, a large population was screened. METHODS: In a Norwegian county, all inhabitants 20 years or older were invited to participate in a population-based health survey programme. Screening for HH was one of several subprojects. Blood samples were obtained from 65,238 persons. Subjects with high serum transferrin saturation in two tests and high serum ferritin were clinically evaluated for HH. All subjects with high serum transferrin saturation in two tests were offered genotyping. RESULTS: HH was newly diagnosed in 92 women and 177 men. Phlebotomy treatment was performed in 64 women and 152 men. Severe organ damage (liver cirrhosis) was ascertained in only 4 men. We found no correlation between serum ferritin and age. The estimated cost was US$ 1.6 per subject screened and US$ 390 per newly discovered HH subject. The estimated prevalence of phenotypical HH not previously known was 0.34% in women and 0.68% in men. The prevalence of the C282Y/C282Y mutation was at least 0.68%. CONCLUSION: Large-scale screening for HH can be performed at a relatively low cost if combined with a health survey programme. The yield in terms of newly discovered cases is considerable, but few cases were found seriously ill. Better knowledge of the natural course of HH is necessary if we are to be able to estimate the cost-effectiveness of large-scale screening.

Adult↗
PubMed2001

Intra- and interhospital repeatability of radionuclide left ventricular ejection fraction in post-infarction patients.

OBJECTIVE: To evaluate intra- and interobserver and interhospital repeatability of radionuclide left ventricular ejection fraction in post-infarction patients. DESIGN: The study comprised 131 patients who were examined in three different hospitals 2-7 days post infarction. The radionuclide examinations were conducted in a standardized manner, and different observers carried out repeated measurements blind on the stored raw data. RESULTS: The coefficients of variation were between 1.5% and 6.2%, and limits of agreement between +/- 0.012 and 0.056. There were no significant differences between the intra- and interobserver or interhospital repeatability in average, but some significant differences between individual observers were noted. CONCLUSION: The repeatability of LVEF was acceptable, with limits of agreement in the range +/- 0.012-0.056. Some differences between observers and hence hospitals were noted, which may be of clinical relevance.

Adult↗
PubMed2001

Better microvascular function on long-term treatment with lisinopril than with nifedipine in renal transplant recipients.

BACKGROUND: The prevalence of hypertension in renal transplant recipients is high but the pathophysiology is poorly defined. Impaired endothelial function may be a factor of major importance. The present study addresses the effects of long-term treatment with either lisinopril or slow-release nifedipine on microvascular function and plasma endothelin in renal transplant recipients on cyclosporin A (CsA). METHODS: Seventy-five hypertensive renal transplant recipients were double-blind randomized to receive slow-release nifedipine (NIF, n=40) or lisinopril (LIS, n=35). Ten normotensive, age-matched recipients served as controls. All patients received CsA-based immunosuppressive therapy including prednisolone and azathioprine. Microvascular function was assessed in the forearm skin vasculature, using laser Doppler flowmetry in combination with post-occlusive reactive hyperaemia and endothelial-dependent function during local acetylcholine (ACh) stimulation. RESULTS: The analysis of microvascular function (AUC(rh)) showed that nifedipine-treated patients had significantly lower responses compared with lisinopril-treated patients (20+/-17 and 43+/-20 AU x min respectively, P=0.0016). Endothelial function was borderline significantly lower in the NIF group compared with the LIS group (640+/-345 and 817+/-404 AU x min respectively, P=0.056). The responses in the LIS group were comparable with those in non-hypertensive controls (AUC(rh) was 37+/-16 and AUC(ACh) was 994+/-566 AU x min). Plasma endothelin-1 concentrations were significantly higher in the NIF group compared with the LIS group (0.44+/-0.19 vs. 0.34+/-0.10 fmol/ml respectively, P=0.048), and were 0.29+/-0.09 fmol/ml in the control patients. AUC(ACh) was associated with plasma endothelin-1 (P=0.0053), while AUC(rh) was not (P=0.080). CONCLUSIONS: The study indicates that long-term treatment with lisinopril, when compared with nifedipine, yields a more beneficial effect on microvascular function in hypertensive renal transplant recipients on CsA. The beneficial microvascular effect may be mediated in part by an endothelin-1-associated effect on the endothelium.

Adult↗
PubMed2001

Atorvastatin improves endothelial function in renal-transplant recipients.

BACKGROUND: Hyperlipidaemia and endothelial dysfunction are common features in cyclosporin A (CsA)-treated renal transplant recipients. Endothelial dysfunction may contribute to the risk of premature atherosclerosis and cardiovascular death in these patients. A beneficial effect of statin therapy beyond cholesterol lowering may be an improvement of endothelial function. The present study was designed to assess the effect of atorvastatin on serum lipids and endothelial function in CsA treated renal transplant recipients. METHODS: This pilot study was an open trial of 4 weeks atorvastatin (10 mg per day) treatment in renal transplant recipients (n=22). All patients received a CsA- and prednisolone-based immunosuppressive regimen. Endothelial function was assessed in the forearm skin microvasculature by acetylcholine stimulation and laser Doppler flowmetry, before and after atorvastatin treatment. Serum lipids, plasma endothelin-1 (ET-1), nitric oxide (NO), and von Willebrand factor (vWF) were also measured. RESULTS: Both total and LDL cholesterol were significantly reduced by 26.8 +/- 8.4 and 41.5 +/- 11.0% respectively, after 4 weeks of treatment. Endothelial function was significantly improved during atorvastatin treatment, area under the flux versus time curve (AUC)(ACh) was 538 +/- 362 AU x min before and 682 +/- 276 AU x min after treatment (P=0.042). Plasma NO levels also showed a borderline significant increase from 49 +/- 30 to 57 +/- 37 micromol/l during the treatment period (P=0.051), though plasma ET-1 (0.37+/-0.08 vs 0.37+/-0.12 fmol/ml) and vW (196+/-57 vs 197+/-37%) were unchanged. CONCLUSION: Atorvastatin lowered serum cholesterol significantly and improved endothelial function in renal transplant recipients after 4 weeks of treatment. Plasma NO levels were increased during atorvastatin treatment, indicating a possible endothelial protective effect through an "endothelial-NO pathway".

Adult↗