The Clinical Utility of Free Thyroxine in Oral Levothyroxine Absorption Testing

ObjectiveOriginal absorption studies for levothyroxine (LT₄) were validated using total thyroxine (TT₄) measurements. Free thyroxine (FT₄) has largely supplanted TT₄ in clinical practice. The objective of our study was to assess the clinical utility of FT₄ in oral LT₄ absorption testing.MethodsIn this retrospective electronic health record analysis, we recorded data of patients who underwent LT₄ oral absorption testing between November 2010 and January 2012 because of persistent hypothyroidism despite a greater than anticipated weight-based dose of LT₄. Patients included had primary hypothyroidism and an absorption test with assessment of both TT₄ and FT₄ measured at times 0, 30, 60, 90, 120, 180, 240, 300, and 360 minutes. The test was conducted with 1 mg (five 200-μg tablets) of Synthroid® after an overnight fast by a standard nonisotopic method.ResultsA total of 10 patients (3 men/7 women) underwent absorption testing. Prior to testing, the median daily LT₄ dose was 250 μg (range, 150 to 350 μg). Three patients were also on liothyronine (10, 20, or 50 μg daily). Based on the calculated amount absorbed, 1 patient demonstrated subnormal absorption, and 9 patients were normal. Median body mass index was 33 kg/m² (range, 21 to 50 kg/m²). Median calculated absorption was 105% (range, 3.7 to 195.6%). The correlation comparing FT₄ and TT₄ was 0.88 (95% confidence interval, 0.56 to 0.97, P < .001), a significant correlation.ConclusionFT₄ and TT₄ correlated highly, even in patients who were severely hypothyroid; FT₄ may be used interchangeably with TT₄ as a qualitative assessment of suspected malabsorption using an oral LT₄ absorption test. (Endocr Pract. 2014;20:925-929)     

Effect of selenium on thyroid hormone metabolism in filial cerebrum of mice with excessive iodine exposure

The effects of supplementing selenium on thyroid hormone metabolism were studied on mice with excessive iodine exposure. The serum concentrations of thyroxine (T₄) and triiodothyronine (T₃) and the activities of iodothyronine 5′ and 5-deiodinase (D2, D3) were measured in the brain of filial mice to study the influence of selenium on thyroid hormone metabolism. Measurements were carried out on postnatal day 0, 14, and 28. It was found that selenium supplementation alleviated the adverse effects of excessive iodine on progeny. The serum TT₄ level as well as TT₄ and TT₃ concentrations and D3 activity in cerebrum of progeny decreased, whereas D2 activity increased in the cerebrum of progeny on postnatal day 0 and 14. Selenium supplementation exerted some favorable effects on thyroid hormone metabolism in cerebrum of progeny of dam with excessive iodine intake.     

Serum T4, T3 and reverse T3 in ethanol fed rats.

To investigate the influence of chronic ethanol consumption on circulating thyroid hormone levels, male and female rats were given 20% ethanol as the only drinking solution daily for 8 weeks. Blood ethanol levels ranged 30–45 mg/L. In male rats serum T₄ decreased from the initial mean ± SD value of 5.2±1.4 to3.0 ±0.7 μg/dl; T₃ decreased from initial value of 97±14 to 66±11 ng/dl and rT₃ decreased from initial value of 19±9 to 10±1 ng/dl after 8 weeks of ethanol ingestion. Under similar experimental conditions, female rats showed a significant decrease in serum T₄ and rT₃ levels; however, T₃ levels decreased slightly but not significantly as compared to initial values. The results indicate adverse effect of chronic ethanol intake on serum thyroid hormone levels in rats.     

Influence of pH, temperature and the cationic porphyrin TMPyP4 on the stability of the i-motif formed by the 5'-(C3TA2)4-3' sequence of the human telomere

The influence of pH, temperature and the cationic porphyrin TMPyP4 on the conformational equilibria of the cytosine-rich strand of the human telomeric sequence 5′-(C₃TA₂)₄-3′, as well as those of the sequence 5′-(C₃TT₂)₄-3′, was studied. The presence of adenine bases at the loops causes the formation of two different intramolecular i-motif structures with a pH-transition midpoint around 4.6, which stability is lower than the i-motif formed by the sequence 5′-(C₃TT₂)₄-3′. The stoichiometries of the complexes formed by these i-motif structures with TMPyP4 are also influenced by the presence of adenine at the loops.     

Monocrotophos Pesticide Decreases the Plasma Levels of Total 3,3′,5-Triiodo-l-Thyronine and Alters the Expression of Genes Associated with the Thyroidal Axis in Female Goldfish (Carassius auratus)

Our recent study showed that monocrotophos (MCP) pesticide disrupted the hypothalamic-pituitary-thyroid (HPT) axis in male goldfish (Carassius auratus); however, the effects of MCP on the thyroid system in female goldfish are remain unclear. In the present study, plasma thyroid hormone (TH) and thyroid-stimulating hormone (TSH) levels were evaluated in female goldfish exposed to 0.01, 0.10, and 1.00 mg/L of 40% MCP-based pesticide for 21 days in a semi-static exposure system. Expression profiles of HPT axis-responsive genes, including transthyretin (ttr), deiodinases (d1, d2, and d3), tshβ, thyrotropin-releasing hormone (trh), and corticotrophin-releasing hormone (crh), were determined. The results indicated that MCP decreased the plasma levels of total 3,3′,5-triiodo-l-thyronine (TT₃) and the ratio of TT₃ to total 3,3′,5,5′-l-thyroxine (TT₄), and induced alternative expression of TH-related genes. Exposure to 0.01 and 0.10 mg/L MCP pesticide resulted in the up-regulation of ttr mRNA. The reduction of plasma TT₃ levels was partly attributed to an increase in the metabolism of T₃ in the liver, as revealed by the highly elevated hepatic d1 and d3 mRNA levels in the MCP treatment groups, and the expression of hepatic d3 showed a negative correlation with the plasma TT₃/TT₄ levels in females. Moreover, the plasma TSH levels were lower in females exposed to 0.01 and 0.10 mg/L MCP pesticide, whereas the up-regulation of tshβ mRNA levels was compensated by the decreased plasma TT₃ levels. These results indicated that MCP had the potential to influence several pathways of HPT axis homeostasis in female goldfish.     

Molecular-mechanical studies of hormone–protein interactions: The interaction of T4 and T3 with prealbumin

We present molecular-mechanical calculations on the interactions of L -thyroxine (T₄) and 3,5,3′-triiodo-L -thyronine (T₃) with the binding site of human serum prealbumin. Energy refinement with restraints on the movement of the iodine atoms leads to reasonably low-energy structures with the iodines within 0.2 Å of their x-ray determined positions; removal of these restraints leads to larger (～1.0 Å) deviations from these positions. However the relative energies of T₃ and T₄ complexation are similar in both cases, and the relative calculated energies for these complexes, when corrected by a simple empirical method for the solvation energy differences of the hormones, are in reasonable qualitative agreement with experiment.     

Evaluation of zinc in the regulation of serum T3 and T4 levels and hepatic functions in carbontetrachloride-intoxicated rats

Circulating tri-iodothyronine (T₃) and thyroxine (T₄) concentrations were determined after 6 wk of zinc treatment to carbontetrachloride (CCl₄) intoxicated male albino rats. Concentrations of T₃ were observed to be significantly depressed following CCl₄ treatment alone. On the contrary, no significant change was noticed in the concentrations of T₄ when compared to controls. However, zinc administration to hepatotoxic animals resulted in restoring the T₃ activity to within normal limits, thus indicating the indirect effects of zinc on the regulation of thyroid hormone concentrations. The activities of all the serum and hepatic marker enzymes were found to be significantly elevated following CCl₄ treatment. However, following zinc supplementation to these intoxicated animals, the levels of the marker enzymes decreased significantly when compared to the CCl₄-treated animals. A similar trend was seen in the case of lipid peroxidation following zinc treatment.     

Biochemical and histomorphological findings in Swiss Wistar rats treated with potential boron-containing therapeutic - K2[B3O3F4OH]

BackgroundBoron and boron containing compounds are known for their biological and protective roles being non-toxic and non-mutagenic in low concentrations. Male rats were exposed to halogenated boroxine (HB), dipotassium-trioxohydroxytetrafluorotriborate K₂[B₃O₃F₄OH], a potential new boron-containing therapeutic, aiming to determine concentrations with no adverse effects on selected serum biochemical parameters and histomorphological features.MethodsHB was prepared by reacting potassium hydrofluoride (KHF₂) with boric acid in molar ratios 2:3 at room temperature and its primary structure contains 4 fluorine atoms substituted in 6-membered ring. In concentrations of 10, 25, 35 and 45 mg/kg, HB was administered intraperitoneally as a single dose. Biochemical parameters were observed 24 and 96 h following the treatment. Effects of HB on biochemical blood parameters were also observed 24 h following continuous nine days application in concentrations of 10 mg/kg intraperitoneally and 50 mg/kg per os. Histomorphological observation of kidneys, liver, spleen, lungs and heart was performed for all treated animals.ResultsAdministration of single high dose of HB (35 mg/kg–45 mg/kg) effected high levels of urea and creatinine, which indicated renal injury that appeared to be temporary. Possible cause of concern is pancreatic injury indicated by elevated levels of serum amylase in the groups of animals that received the highest dosages of the substance. Histopathological examination of selected tissues revealed mild to moderate lesions in the kidneys and livers associated with administration of HB.ConclusionObservation of biochemical serum parameters or histopathology of examined tissues revealed no adverse effects of HB either after the administration of single dose lower than 35 mg/kg or following repeated administration at 10 mg/kg. These dosages should be further considered for potential therapeutic applications.     

Influence of short-term glucocorticoid therapy on regulatory T cells in vivo

Background

Pre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(T_reg) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs).

Objective

We readdressed the influence of GC therapy on T_reg cells in immunocompetent human subjects and naïve mice.

Methods

Mice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and T_reg cells in spleen and blood were analyzed by FACS. Sixteen patients with sudden hearing loss but without an inflammatory disease received high-dose intravenous prednisolone followed by stepwise dose reduction to low oral prednisolone. Peripheral blood T_reg cells were analyzed prior and after a 14 day GC therapy based on different markers.

Results

Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of T_reg cells in blood (100 mg dexamethasone/kg body weight: 2.8±1.8×10⁴ cells/ml vs. 33±11×10⁴ in control mice) and spleen (dexamethasone: 2.8±1.9×10⁵/spleen vs. 95±22×10⁵/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3⁺ T_reg cells amongst the CD4⁺ T cells also decreased in a dose dependent manner with the effect being more pronounced in blood than in spleen. The suppressive capacity of T_reg cells was unaltered by GC treatment in vitro. In immunocompetent humans, GCs induced mild T cell lymphocytosis. However, it did not change the relative frequency of circulating T_reg cells in a relevant manner, although there was some variation depending on the definition of the T_reg cells (FOXP3⁺: 4.0±1.5% vs 3.4±1.5%*; AITR⁺: 0.6±0.4 vs 0.5±0.3%, CD127^low: 4.0±1.3 vs 5.0±3.0%* and CTLA4+: 13.8±11.5 vs 15.6±12.5%; * p<0.05).

Conclusion

Short-term GC therapy does not induce the hitherto supposed increase in circulating T_reg cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating T_reg cell numbers.     

Pyrroloquinoline quinone ameliorates l‐thyroxine‐induced hyperthyroidism and associated problems in rats

Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant. In this study, we have evaluated its hitherto unknown role in l ‐thyroxin (L‐T₄)‐induced hyperthyroidism considering laboratory rat as a model. Alterations in the serum concentration of thyroxin (T₄) and triiodothyronine (T₃); lipid peroxidation (LPO) of liver, kidney, heart, muscles and brain; in the endogenous antioxidants such as superoxide dismutase, catalase and glutathione and in serum total cholesterol, high‐density lipoprotien, triglycerides, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and urea were evaluated. Administration of l ‐T₄ (500‐µg kg^?1 body weight) enhanced not only the serum T₃ and T₄ levels but also the tissue LPO, serum SGOT, SGPT and urea with a parallel decrease in the levels of antioxidants and serum lipids. However, on simultaneous administration of PQQ (5 mg kg^?1 for 6 days), all these adverse effects were ameliorated, indicating the potential of PQQ in the amelioration of hyperthyroidism and associated problems. Possibly, the curative effects were mediated through inhibition of oxidative stress. We suggest that PQQ may be considered for therapeutic use for hyperthyroidism after dose standardization. Copyright © 2014 John Wiley & Sons, Ltd.     

Serum Thyrotropin in Graves’ Disease: A More Reliable Index of Circulating Thyroid-Stimulating Immunoglobulin Level than Thyroid Function?

ObjectiveTo assess the relationship between serum thyrotropin (thyroid-stimulating hormone or TSH) on one hand and thyroid-stimulating immunoglobulin (TSI), free thyroxine (T₄), and triiodothyronine (T₃) levels on the other in Graves’ disease, inasmuch as TSH may be suppressed in the presence of TSI because TSI may bind to the TSH receptor on the thyroid gland membrane and thus eliminate the need for circulating TSH for stimulating the thyroid gland.MethodsWe determined serum TSI levels in 37 women and 13 men with Graves’ disease, stratified into 4 groups on the basis of serum TSH levels irrespective of serum free T₄ and T₃ levels. Our reference ranges were 0.72 to 1.74 ng/dL for free T₄, 80 to 200 ng/dL for T₃, and to 4.0 μU/mL for TSH.ResultsMean serum TSI concentrations were highest (215% ± 28%) in patients with undetectable TSH levels (< 0.03 μU/mL) and lowest (103% ± 9%) in those with supernormal TSH concentrations (> 4.0 μU/mL). TSI levels were intermediate in the other study groups: 157% ± 16% in patients with subnormal though detectable TSH levels (0.03 to 0.39 μU/mL) and 125% ± 12% in those with normal TSH levels (0.4 to 4.0 μU/mL). Moreover, a progressive decline in TSI levels with increasing serum TSH concentrations was noted, along with a significant negative correlation (r = -0.45; P < 0.01) between serum TSI and TSH concentrations. Finally, relationships between free T₄ and T₃ levels on one hand and TSI or TSH levels on the other were not significant, with a considerable variability in free T₄ and T₃ levels being noted in individual study groups.ConclusionSerum TSH is frequently suppressed after treatment with antithyroid drugs or radioiodine (¹³¹I), irrespective of clinical thyroid function as expressed by increased, normal, or decreased free T₄ and T₃ concentrations. In an individual patient with Graves’ disease, the serum TSH level may be more reflective of the circulating TSI concentration than is thyroid gland function as expressed by free T₄ and T₃ concentrations and therefore may be as reliable a predictor of remission as TSI. (Endocr Pract. 2007;13:615-619)     

The effect of feeding on CO2 production and energy expenditure in ponies measured by indirect calorimetry and the 13C-bicarbonate technique

Energy expenditure (EE) can be estimated based on respiratory gas exchange measurements, traditionally done in respiration chambers by indirect calorimetry (IC). However, the ¹³C-bicarbonate technique (¹³C-BT) might be an alternative minimal invasive method for estimation of CO₂ production and EE in the field. In this study, four Shetland ponies were used to explore the effect of feeding on CO₂ production and EE measured simultaneously by IC and ¹³C-BT. The ponies were individually housed in respiration chambers and received either a single oral or intravenous (IV) bolus dose of ¹³C-labelled sodium bicarbonate (NaH¹³CO₃). The ponies were fed haylage 3 h before (T₋₃), simultaneously with (T₀) or 3 h after (T₊₃) administration of ¹³C-bicarbonate. The CO₂ produced and O₂ consumed by the ponies were measured for 6 h with both administration routes of ¹³C-bicarbonate at the three different feeding times. Feeding time affected the CO₂ production (P<0.001) and O₂ consumption (P<0.001), but not the respiratory quotient (RQ) measured by IC. The recovery factor (RF) of ¹³C in breath CO₂ was affected by feeding time (P<0.01) and three different RF were used in the calculation of CO₂ production measured by ¹³C-BT. An average RQ was used for the calculations of EE. There was no difference between IC and ¹³C-BT for estimation of CO₂ production. An effect of feeding time (P<0.001) on the estimated EE was found, with higher EE when feed was offered (T₀ and T₊₃) compared with when no feed was available (T₋₃) during measurements. In conclusion, this study showed that feeding time affects the RF and measurements of CO₂ production and EE. This should be considered when the ¹³C-BT is used in the field. IV administration of ¹³C-bicarbonate is recommended in future studies with horses to avoid complex ¹³C enrichment-time curves with maxima and shoulders as observed in several experiments with oral administration of ¹³C-bicarbonate.     

Pharmacokinetics of oral moxidectin in individuals with Onchocerca volvulus infection

BackgroundOnchocerciasis (“river blindness”), is a neglected tropical disease caused by the filarial nematode Onchocerca volvulus and transmitted to humans through repeated bites by infective blackflies of the genus Simulium. Moxidectin was approved by the United States Food and Drug Administration in 2018 for the treatment of onchocerciasis in people at least 12 years of age. The pharmacokinetics of orally administered moxidectin in 18- to 60-year-old men and women infected with Onchocerca volvulus were investigated in a single-center, ivermectin-controlled, double-blind, randomized, single-ascending-dose, ascending severity of infection study in Ghana.Methodology/Principal findingsParticipants were randomized to either a single dose of 2, 4 or 8 mg moxidectin or ivermectin. Pharmacokinetic samples were collected prior to dosing and at intervals up to 12 months post-dose from 33 and 34 individuals treated with 2 and 4 mg moxidectin, respectively and up to 18 months post-dose from 31 individuals treated with 8 mg moxidectin. Moxidectin plasma concentrations were determined using high-performance liquid chromatography with fluorescence detection. Moxidectin plasma AUC_0-∞ (2 mg: 26.7–31.7 days*ng/mL, 4 mg: 39.1–60.0 days*ng/mL, 8 mg: 99.5–129.0 days*ng/mL) and C_max (2mg, 16.2 to17.3 ng/mL, 4 mg: 33.4 to 35.0 ng/mL, 8 mg: 55.7 to 74.4 ng/mL) were dose-proportional and independent of severity of infection. Maximum plasma concentrations were achieved 4 hours after drug administration. The mean terminal half-lives of moxidectin were 20.6, 17.7, and 23.3 days at the 2, 4 and 8 mg dose levels, respectively.Conclusion/SignificanceWe found no relationship between severity of infection (mild, moderate or severe) and exposure parameters (AUC_0-∞ and C_max), T_1/2 and T_max for moxidectin. T_max, volume of distribution (V/F) and oral clearance (CL/F) are similar to those in healthy volunteers from Europe. From a pharmacokinetic perspective, moxidectin is an attractive long-acting therapeutic option for the treatment of human onchocerciasis.     

Immunostimulating effect of triiodothyronine: dietary administration of triiodothyronine in rohu (Labeo rohita) enhances immunity and resistance to Aeromonas hydrophila infection

The immunomodulatory effects of dietary administration of 3,3^′,5‐triiodo‐l ‐thyronine (T₃) at 0, 1, 5 and 10 mg  kg^?1 of diet for 60 days in rohu (Labeo rohita) fingerlings were studied. Oral administration of T₃ at all dose levels resulted in significantly (P<0.05) higher serum T₃ levels, total serum protein and globulin levels, and reduced albumin–globulin ratio (A : G) compared with the control group, whereas feeding of T₃ at 5 and 10 mg kg^?1 diet enhanced the growth and superoxide production by neutrophils. At the end of the 60‐day experimental period the optimum dosage of T₃ appeared to be the 5 mg  kg^?1 diet for rohu fingerlings, resulting in a significantly higher specific antibody titre against formalin‐killed Aeromonas hydrophila and lowering the mortality percentage against the A. hydrophila challenge.     

Parasitic Nematode-Induced CD4+Foxp3+T Cells Can Ameliorate Allergic Airway Inflammation

Background

The recruitment of CD4⁺CD25⁺Foxp3⁺T (T_reg) cells is one of the most important mechanisms by which parasites down-regulate the immune system.

Methodology/Principal Findings

We compared the effects of T_reg cells from Trichinella spiralis-infected mice and uninfected mice on experimental allergic airway inflammation in order to understand the functions of parasite-induced T_reg cells. After four weeks of T. spiralis infection, we isolated Foxp3-GFP-expressing cells from transgenic mice using a cell sorter. We injected CD4⁺Foxp3⁺ cells from T. spiralis-infected [Inf(+)Foxp3⁺] or uninfected [Inf(-)Foxp3⁺] mice into the tail veins of C57BL/6 mice before the induction of inflammation or during inflammation. Inflammation was induced by ovalbumin (OVA)-alum sensitization and OVA challenge. The concentrations of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and the levels of OVA-specific IgE and IgG1 in the serum were lower in mice that received intravenous application of Inf(+)Foxp3⁺ cells [IV(inf):+(+) group] than in control mice. Some features of allergic airway inflammation were ameliorated by the intravenous application of Inf(-)Foxp3⁺ cells [IV(inf):+(-) group], but the effects were less distinct than those observed in the IV(inf):+(+) group. We found that Inf(+)Foxp3⁺ cells migrated to inflammation sites in the lung and expressed higher levels of T_reg-cell homing receptors (CCR5 and CCR9) and activation markers (Klrg1, Capg, GARP, Gzmb, OX40) than did Inf(-)Foxp3⁺ cells.

Conclusion/Significance

T. spiralis infection promotes the proliferation and functional activation of T_reg cells. Parasite-induced T_reg cells migrate to the inflammation site and suppress immune responses more effectively than non-parasite-induced T_reg cells. The adoptive transfer of Inf(+)Foxp3⁺ cells is an effective method for the treatment and prevention of allergic airway diseases in mice and is a promising therapeutic approach for the treatment of allergic airway diseases.     

经皮穴位电刺激对老年髋关节置换术患者脑氧代谢以及术后认知功能、镇痛效果的影响

目的:探讨经皮穴位电刺激(TEAS)对老年髋关节置换术患者脑氧代谢以及术后认知功能、镇痛效果的影响。方法:选取2016年1月～2018年7月期间我院收治的行髋关节置换术患者91例为研究对象,将研究对象根据随机数字表法分为对照组(n=45)和研究组(n=46),对照组给予常规麻醉处理,研究组在对照组基础上给予TEAS,比较两组脑氧代谢、术后认知功能以及镇痛效果,记录两组术后的不良反应发生情况。结果:在降压开始后20 min(T1)、降压开始后40 min(T2)、停止降压后20 min(T3)时间点时,两组静脉血氧含量(Cjv O2)较降压前即刻(T0)时间点升高,且研究组高于对照组(P0.05),两组脑动-静脉血氧含量差(Da-jvO2)、脑氧摄取率(CERO2)较T0时间点降低,且研究组低于对照组(P0.05)。两组患者术后72h简易智能量表(MMSE)评分均较术前24h降低,但研究组高于对照组(P0.05),研究组术后认知功能障碍(POCD)发生率低于对照组(P0.05)。与术前比较,两组患者术后8h、术后24h、术后48h视觉疼痛模拟量表(VAS)评分均升高(P0.05),但研究组术后8h、术后24h、术后48h等时间点VAS评分均低于对照组(P0.05)。两组患者不良反应总发生率比较无差异(P0.05)。结论:TEAS对老年髋关节置换术后患者的镇痛效果确切,可有效改善脑氧代谢情况,提高术后认知功能,临床应用价值较高。     

Inhibition of platelet function by abciximab or high-dose tirofiban in patients with STEMI undergoing primary PCI: a randomised trial

BackgroundIn patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI, few data exist on the magnitude of platelet activation, aggregation and dosing of glycoprotein (GP) IIb/IIIa receptor inhibitors. Methods Sixty STEMI patients were randomised to abciximab, to high-dose tirofiban or to no additional GP IIb/IIIa inhibitor treatment. Platelet activation (P-selectin expression) was measured using flow cytometry and the level of inhibition of platelet aggregation was assessed using the Plateletworks assay. Additionally, the PFA-100 with the collagen/adenosine-diphosphate cartridge (CADP) was used to compare the levels of platelet inhibition. All measurements were performed at baseline (T₀), immediately after (T₁), 30 minutes (T₂), 60 minutes (T₃) and 120 minutes (T₄) after primary PCI. Results The level of platelet activation in both GP IIb/IIIa receptor inhibitor treated groups was significantly lower compared with the control group at all time points after primary PCI (p=0.04). Also the administration of the currently recommended dose of abciximab resulted in significantly lower levels of inhibition of aggregation compared with high-dose tirofiban (p<0.0001). In addition, the CADP closure times were significantly prolonged in both GP IIb/IIIa inhibitor treated groups compared with the control group at time points T1 (p=0.006) and T4 (p<0.0001). Conclusion The administration of high-dose tirofiban resulted in a significantly higher inhibition of platelet aggregation compared with the currently recommended dose of abciximab. Large clinical trials are needed to assess whether this laboratory superiority of high-dose tirofiban translates into higher clinical efficacy. (Neth Heart J 2007;15:375-81.)