Prospective Assessment of Hepcidin in Relation to Delayed or Immediate Graft Function in Patients Undergoing Kidney Transplantation.

BACKGROUND: Hepcidin is a peptide hormone that regulates iron homeostasis. Hepcidin may represent an early, predictive biomarker of acute kidney injury, another model of ischemia-reperfusion injury. Urinary hepcidin-25 has been shown to be elevated in patients who do not develop acute kidney injury. Creatinine is an unreliable indicator during acute changes in kidney; therefore, the aim of the study was to assess whether hepcidin could predict renal outcome in 31 consecutive patients undergoing kidney allograft transplantation. Serum hepcidin was evaluated before and after 1, 3, 6, and 10 days after kidney transplantation, using commercially available kits. Serum creatinine was assessed at the same time. METHODS: We found a significant decrease in serum hepcidin, as early as after 1 day after kidney transplantation. Before transplantation, serum hepcidin was related to creatinine. In patients with delayed graft function, there was no decrease in serum hepcidin. RESULTS: Our findings may have important implications for the clinical treatment of patients undergoing kidney transplantation. The "window of opportunity" is narrow in delayed graft function to distinguish between acute rejection and calcineurin inhibitors nephrotoxicity, and time is limited to introduce proper treatment after initiating insult. CONCLUSIONS: Hepcidin must be investigated as a potential early marker for delayed graft function, especially in the upcoming setting of early dialysis treatment or anti-rejection therapy and might contribute to early patient risk stratification.

Expression of VEGFs and its receptors in abdominal aortic aneurysm.

AIM: The development of abdominal aortic aneurysm (AAA) is thought to be related to an imbalance of VEGF and its receptors. This study aimed at evaluating the expression of VEGF family members and their receptors in AAA wall, AAA mural thrombus and normal aorta wall. METHODS: AAA specimens (mural thrombus-luminal layer, mural thrombus-abluminal layer, AAA wall) were collected from 24 patients undergoing elective open AAA repair. Abdominal aortas from 12 organ donors served as controls. The expression of VEGF (VEGF-A, VEGF-B, VEGF-C and VEGF-D) and VEGF receptors (VEGFR-1, VEGFR-2 and VEGFR-3) was evaluated using Western blot. RESULTS: Increased expression of VEGF-B (269±31%), VEGF-C (1065±92%) and VEGF-D (145±12%) was found in AAA wall, when compared to normal aorta (P<0.01). No significant difference in VEGF-A expression was demonstrated between AAA and normal aortic wall (P>0.01). Mural thrombus (abluminal/luminal) expression of VEGF-A (172±22%/133±17%), VEGF-B (308±24% / 363±28%), VEGF-C (1496±110%/830±58%) and VEGF-D (200±18%/142±12%) was increased in comparison with normal aorta (P<0.01). Furthermore, VEGF-C and VEGF-D expression was increased in mural thrombus abluminal layer, when compared to its luminal layer (1496±110% vs. 830±58% and 200±18% vs. 142±12%, P<0.01). VEGFR-1 expression was increased only in luminal and abluminal layers of mural thrombus (377±58% and 2188±196%, P<0.01). In comparison with normal aorta, all aneurysm samples (AAA wall, mural thrombus abluminal and luminal layers) expressed higher levels of VEGFR-2 (565±52%, 1057±125%, 537±54%, P<0.01) and VEGFR-3 (233±18%, 197±17%, 193±16%, P<0.01). CONCLUSIONS: Our study demonstrates that the abluminal layer in AAA mural thrombus contains high levels of VEGFs and VEGF receptors, suggesting that this layer may play a significant role in AAA disease pathogenesis. Increased expressions of VEGF and their receptors in AAA mural thrombus may impact different pathways involved in AAA etiology.

Associations between IQ and alcohol consumption in a population of young males: a large database analysis.

PURPOSE: This study aimed at exploring the relationship between intelligence quotient (IQ) and alcohol consumption in a large sample of young males. This study explored whether IQ influences alcohol drinking and which pathways might be involved. We further hypothesized that IQ differences between lifetime abstainers and former drinkers exist, and that they primarily result from different group characteristics. METHOD: Within a psychiatric-epidemiological survey using a cross-sectional design IQ-tests were administered to approximately 50,000 Swiss conscripts at age of about 20 years. The sample was divided into four alcohol consumption categories (rare, occasional, moderate and daily drinking) and two non-drinker categories (former drinking and lifetime abstinence). Probabilities for different levels of consumption or former drinking against lifetime abstention in relation to IQ were estimated using multinomial logistic regression. Models were adjusted for education, disability pension, tobacco/cannabis use, migration, parental alcohol disorders, and mental health. RESULTS: After adjusting for confounders full-scale IQ displayed positive associations with being a rare (OR 1.13; CI 95 % 1.07-1.19), occasional (OR 1.41; CI 95 % 1.33-1.48), and moderate drinker (OR 1.53; CI 95 % 1.45-1.62), and negative associations with being a former drinker (OR 0.85; CI 95 % 0.79-0.93). Daily drinking was positively associated only with the performance subscale IQ (OR 1.12; CI 95 % 1.02-1.22). Confounders contributed significantly to the IQ-alcohol association and, therefore, highlight the distinction of non-drinkers into lifetime abstainers and former drinkers. CONCLUSIONS: Our data confirmed the positive link between IQ and moderate drinking. Lower IQ in non-drinkers, however, seems to be related to earlier consumption and the presence of other risk factors.

Neuraxial anesthesia for cardiac surgery: thoracic epidural and high spinal anesthesia - why is it different?

Anesthesiologists can offer much more then stable blood pressure and heart rate in the intraoperative period. By choosing appropriate anesthetic techniques they can tremendously influence perioperative stress. This may positively impact on the overall surgical outcome. One of the most intriguing aspects of neuraxial anesthesia is its ability to attenuate the stress response to surgery. At present there is no agreement on the clinical importance of such a response but there is substantial indirect evidence that it may play an important role in a patient's outcome. Neuraxial anesthesia supplemented by general anesthesia is justified and can be safely used in cardiac surgery. The authors of this expert opinion prefer spinal anesthesia to thoracic epidural anesthesia and have been using it routinely for the last 20 years without any neurological complications. The risk of spinal hematoma from a 27G spinal needle prior to full heparinization is unknown but in our opinion is remote. Both epidural and spinal techniques can and should have a place in modern cardiac anesthesia practice and should be further investigated.

Neutrophil gelatinase-associated lipocalin and cystatin C could predict renal outcome in patients undergoing kidney allograft transplantation: a prospective study.

Urinary neutrophil gelatinase-associated lipocalin (NGAL) may represent an early, predictive biomarker of delayed graft function due to ischemia-reperfusion injury. Unfortunately, creatinine is an unreliable indicator of acute changes in kidney function. NGAL was proposed as a novel early marker for detection of acute renal failure. Therefore, the aim of the study was to assess whether NGAL and cystatin C predicted outcomes among 41 consecutive patients undergoing kidney transplantation. Serum NGAL and cystatin C were evaluated before, as well as 1, 3, 6, and 10 days after kidney transplantation using commercially available kits. Serum creatinine was assessed at each time. We observed a significant fall in serum NGAL as early as 1 day following kidney transplantation. Serum cystatin C decreased significantly 3 days after transplantation. Before transplantation, serum NGAL was related to creatinine and cystatin C. At each time point, serum NGAL was related positively to serum creatinine, cystatin C, and negatively to urine volume. In patients with delayed graft function, there was no fall in serum NGAL or cystatin C. Our findings may have important implications for the clinical management of patients undergoing kidney transplantation. The "window of opportunity" to distinguish between acute rejection and calcineurin inhibitor nephrotoxicity is narrow in delayed graft function. Time is limited to introduce proper treatment after the initiating insult. Therefore, NGAL needs to be investigated as a potential early marker for delayed graft function, especially in the settings of early dialysis treatment or antirejection therapy.

Glycosaminoglycan-degrading enzymes in the varicose vein wall.

AIM: Mechanical properties of the vein wall are determined by extracellular matrix components, including glycosaminoglycans (GAGs). The aim of the study was to evaluate the activity of enzymes involved in GAGs degradation pathway in the wall of varicose veins and varicose veins complicated by thrombophlebitis, when compared to the wall of normal ones. METHODS: Normal, varicose veins and varicose veins complicated by thrombophlebitis were collected during surgical treatment of 10 patients. Activities of endoglycosidases, sulphatases and exoglycosidases were assessed according to colorimetric methods. RESULTS: Activities of neutral endoglycosidases degrading chondroitin-4-sulphate (C4S) and heparan sulphate (HS) were decreased, whereas activities of neutral endoglycosidases degrading dermatan sulphate and hyaluronic acid were increased in varicose veins and varicose veins complicated by thrombophlebitis. Activities of acidic endoglycosidases degrading C4S and HS were decreased in varicose veins and varicose veins complicated by thrombophlebitis, whereas activity of acidic endoglycosidases degrading chondroitin-6-sulphate was decreased only in varicose veins complicated by thrombophlebitis. Furthermore increased activities of arylosulphatase B, beta-N-acetylhexosaminidase and alpha-L-iduronidase were demonstrated in varicose veins, as well as in varicose veins complicated by thrombophlebitis. CONCLUSIONS: Changed activities of GAGs-degrading enzymes may contribute to previously reported changes in the content and molecular differentiation of GAGs in the wall of varicose veins that may play a role in the disease pathogenesis.

The predictive value of arterial renal blood flow parameters in renal graft survival.

BACKGROUND: Renal allograft survival depends on a number of factors, however, no reliable simple parameter has been shown to predict long-term outcome after transplantation. Ultrasound is recognized and relatively inexpensive, providing information about renal location, contour, and size. Doppler ultrasonography shows kidney morphology and hemodynamics. The aim of this study was the evaluation of whether Doppler ultrasound of renal arteries performed in the early stage after transplantation was a valuable predictor for long-term-outcomes. MATERIAL AND METHODS: The study included 17 female and 24 male patients, aged 17-69 years with stable graft function. The Doppler ultrasound of renal flow was done on the 1st and 3rd day after transplantaion, and estimated glomerular filtration rate (eGFR) on the 20th day. The measured indices were as follows: maximum blood flow velocity (V(max)), minimum blood flow velocity (V(min)), resistive index (RI), and pulsatile index (PI). The creatinine concentration was evaluated, and eGFR calculated. RESULTS: Mean renal and intrarenal artery RI increased to day 3 after transplantation, and then reduced. The mean renal and intrarenal V(max) at day 3 correlated positively with eGFR (r = 0.38; P = .015); (r = 0.45; P = .003, respectively). Mean renal and intrarenal V(min) correlated positively with eGFR (r = 0.50; P = .001; r = 0.41; P = .008, respectively). The mean renal and intrarenal V(max) and V(min) on day 1 did not correlate with eGFR. CONCLUSIONS: Early Doppler Ultrasonography of renal graft hemodynamics may be a valuable predictor of graft survival and long-term outcomes. Blood flow velocity within renal arteries seemed to be an important factor.

Renal artery resistance index, thyroid hormones, and thyroid volume in the early kidney transplants recipients.

BACKGROUND: Thyroid hormones could affect renal function, and, on the other hand, renal dysfunction may affect thyroid function. Disturbances of concentrations of thyroid hormones are often associated with thyroid gland enlargement. The aim of the study was to assess the function and morphology of the thyroid (volume and hormones concentration) and kidney function after transplantation (creatinine concentration and resistance index [RI] of transplant artery). MATERIAL AND METHODS: The group included 13 females, 19 males; aged 19-69 years, mean 44.75 +/- 14.8 years after transplantation with stable graft function. Thyroid volume, renal artery RI, creatinine concentration, and concentrations of T3, rT3, FT3, FT4, and TSH were estimated the day before surgery, and at 1, 3, 6, and 10 days after transplantation. RESULTS: The statistical analysis revealed a negative correlation between delta RI (difference between RI at 3 and 6 days after transplantation) and serum creatinine concentration, 10 days after transplantation (r = -0.63; P < 0.01). We also observed a negative correlation between creatinine serum concentration at 10 days after transplantation and delta thyroid volume (Delta Vol; r = - 0.48; p < .05), a positive correlation between delta FT4 (Delta FT4) serum concentration, and delta creatinine (Delta Crea; r = 0.73; P < .001). CONCLUSIONS: The dynamics of RI changes in the transplant kidney artery between 3 and 6 days after transplantation may predict graft function. Together with improved kidney function at 10 days after transplantation, we observed a regression of goiter.

Activity of coagulation and fibrinolytic system components in the vein thrombus.

PURPOSE: Behaviour of the vein thrombus is determined by the activity ratio of coagulation factors to factors of fibrinolytic system. The aim of the study is to evaluate activity of some coagulation and fibrinolytic factors in the vein thrombus. MATERIAL AND METHODS: The activity of platelets aggregating factors, tissue factor, thrombin, antithrombins, antiheparin factors, plasminogen activators, plasmin (plasminogen) and antiplasmins of the vein thrombus homogenate was determined using coagulative, fibrinolytic and caseinolytic tests. Retracted blood clot was a compared material. RESULTS: Tissue factor activity in the vein thrombus was above twofold higher and antiheparin activity was nearly twice higher in comparison to the blood clot. The vein thrombus contains also active thrombin. Plasminogen activators activity in the vein thrombus was twofold higher and activity of plasmin (plasminogen) was threefold higher than in the blood clot. High activity of the tissue factor, substances neutralizing heparin and presence of thrombin intensify the thrombus enlargement. However, the thrombotic tendency may be balanced by a high activity of plasminogen activators and high activity of plasmin (plasminogen). CONCLUSIONS: 1) Vein thrombus is characterized by high activity of tissue factor, presence of active thrombin and high antiheparin activity. 2) High coagulative potential of vein thrombus is balanced to a certain grade by high fibrinolytic potential: high activity of plasminogen activators and high activity of plasmin (plasminogen), as well as absence of antiplasmins activity.

Matrix metalloproteinases in the vein wall.

AIM: Matrix metalloproteinases contribute to extracellular matrix remodelling that can influence mechanical properties of the vein wall and predispose to varicose veins development. The aim of the study was to assess the following matrix metalloproteinases in the wall of varicose veins: tissue collagenase I (MMP-1), gelatinase A (MMP-2), gelatinase B (MMP-9) and stromelysin 1 (MMP-3). METHODS: Normal, varicose and varicose veins complicated by thrombophlebitis were collected during the surgical treatment of 26 patients. In harvested tissues the presence of gelatinases was detected with zymography, contents of MMP-1, MMP-2, MMP-3 and MMP-9 were evaluated with ELISA, activity of MMP-1 was assessed with HPLC and activity of MMP-2 with ELISA. RESULTS: Zymography demonstrated particularly high contents of both gelatinases in the wall of varicose veins complicated by thrombophlebitis. The contents of MMP-1, MMP-2 and MMP-9 were significantly increased only in the wall of varicose veins complicated by thrombophlebitis, whereas the increased content of MMP-3 was also found in the wall of varicose veins. A significantly higher activity of MMP-1 was shown only in the wall of varicose veins complicated by thrombophlebitis, whereas an active form of MMP-2 was increased in the wall of varicose, as well as varicose veins complicated by thrombophlebitis, when compared with normal ones. CONCLUSION: The wall of varicose veins, particularly those complicated by thrombophlebitis shows extensive alterations in the content and activity of matrix metalloproteinases, that may result in extracellular matrix remodelling, influence mechanical properties of the vein wall and predispose to further progression of the disease.

Chemical compound content and enzyme activity in supernatant and sediment of liver homogenate.

Evaluation was performed of chemical compound contents and enzyme activities in the whole homogenate, its supernatant and sediment. Six rabbit livers were pulverized in liquid nitrogen and homogenized. After centrifugation, the contents of protein, haemoglobin, vitamin A, vitamin E, vitamin C, as well as the activities of cathepsin B, cathepsin D, superoxide dismutase, catalase, glutathione peroxidase and reductase were assessed in the whole homogenate, its supernatant and sediment. Protein, vitamin A, superoxide dismutase, catalase, cathepsin D, glutathione peroxidase and reductase reveal uniform localisation. Vitamin C and cathepsin B are localized in supernatant, whereas haemoglobin is localized mainly in sediment. Evaluation of chemical compounds and enzyme activities should be performed in the whole homogenate, supernatant and sediment to obtain a real interpretation of biochemical disturbances in the investigated material.

Assessment of connective tissue fibres in walls of allogenic arterial grafts preserved by the method of cold ischemia--a preliminary report.

The aim of the study was to evaluate microscopic changes in the wall structures of allogenic arterial grafts, preserved by the method of cold ischemia in relation to the storage period and to test the possibility of the storage period prolongation by allograft freezing at -70 degrees C. The middle layer ultrastructure is well preserved till 30 days from allograft harvesting, however, allograft freezing results in total destruction of elastic and collagen fibres in the arterial wall. An application of allogenic arterial grafts, preserved by the method of cold ischemia till 30 days from their harvesting, seems an efficient therapeutic method in the treatment of patients with synthetic vascular graft infection. Further prolongation of the storage period at -70 degrees C made the allograft useless for implantation.

Some components of oxidative-antioxidative system in human blood plasma and serum.

Comparison of the concentrations and activities of components in the oxidative-antioxidative system between blood plasma and serum. Blood plasma and serum samples were obtained from 38 healthy adults to evaluate malondialdehyde concentration, the total antioxidative capacity, superoxide dismutase activity, protein and non-protein sulphydryl groups, ascorbate, haemoglobin, methaemoglobin and protein. Blood plasma shows higher activity of superoxide dismutase, as well as higher concentrations of low-molecular sulphydryl groups and ascorbate, when compared to those in blood serum. The total plasma antioxidative capacity is also higher than that assessed in blood serum. Processes of blood coagulation and blood clot retraction lead to antioxidant consumption. The evaluation of oxidative-antioxidative system for diagnostic purposes should be performed in blood plasma.

Haemoglobin of varicose vein, varicose vein with thrombophlebitis and in parietal thrombus of varicose vein.

Saphenous veins were taken for examination: unchanged, varicose with thrombophlebitis and varicose thrombus. The contents of haemoglobin and protein were determined in the homogenate of that material. Only small quantities of haemoglobin were found in walls of unchanged veins. Greater amounts of haemoglobin were observed in walls of varicose veins, especially in walls of varicose veins with thrombophlebitis. The varicose vein thrombus also contained marked quantities of haemoglobin.

Glycosaminoglycans of normal veins and their alterations in varicose veins and varicose veins complicated by thrombophlebitis.

The aim of the study was to examine the content and molecular differentiation of glycosaminoglycans (GAGs) in the wall of varicose veins. The studied material consisted of normal, varicose veins and varicose veins complicated by thrombophlebitis collected during operations on 26 patients. In the wall of varicose veins the mean GAGs' content as well as the content of sulphated GAGs, except heparan sulphate was increased, whereas the amount of hyaluronic acid was decreased. Furthermore, the increased quantitative ratio between sulphated and nonsulphated GAGs was demonstrated. The results indicate an evident extracellular matrix remodelling in the wall of varicose veins particularly those complicated by thrombophlebitis, that is characterised by alterations in the content and molecular differentiation of GAGs.

New ambulatory impedance cardiograph validated against the Minnesota Impedance Cardiograph.

The validity and reliability of a new ambulatory impedance cardiograph (AZCG) was tested against the Minnesota Impedance Cardiograph (ZCG) during rest, orthostasis, and mental stress. Impedance cardiography allows noninvasive assessment of stroke volume, cardiac output, and systolic time intervals. A reliable ambulatory device would allow studies outside the lab. The devices were compared at two sites in healthy subjects. In both studies, the AZCG tracked changes across conditions closely with the ZCG (all Period x Device interactions were nonsignificant). Pearson rs, were .65 to .93, random intraclass correlation coefficients ranged from .80 to .98, indicating high degrees of shared measurement variance, and Cronbach's alpha indicated very good internal reliabilities (.91 to .99). Relative to the ZCG, the new AZCG appears to provide valid and reliable estimates of cardiac function at rest and during behavioral challenges in the lab.

Effects of changing stance conditions on anticipatory postural adjustment and reaction time to voluntary arm movement in humans.

1. The effect on reaction time (RT) and anticipatory postural adjustment (APA) of unexpectedly changing stance conditions was studied using a push or pull arm movement task. The aim was to evaluate the modifiability of RT and APA by an external perturbation associated with an automatic compensatory reaction. 2. Subjects standing on a moveable platform were asked to push or pull a rigid handle as quickly and as strongly as possible in response to the 'go-signal', a visual signal from a green or red light-emitting diode. Forward and backward translations of the platform were randomly induced at four time intervals after the go-signal. In some experiments to detect unspecific arousal there were no platform translations but an acoustic signal was given before the go-signal. Surface electromyographic activity (EMG) of upper arm and lower leg muscles was analysed. 3. During the push task both RT and the duration of APA (onset of APA till the force signal indicating hand action) were shorter during backward than during forward translation. During the pull task the effect of platform translations was the reverse. The delay between go-signal and onset of APA remained constant. Consequently, RT and APA became shorter when the platform was translated in the same direction as that in which the upper body was displaced by the push or pull movement, and longer when it was translated in the opposite direction. The effects were maximal when translations were induced 250 ms after the go-signal, but a difference was detected up to 375 ms. 4. Furthermore, with forward and backward platform translations RT was shorter when the translations were induced early rather than late after the go-signal. This was associated with a shortening of the delay between the go-signal and onset of APA, while APA duration remained constant. The shortened RT was in the range of that obtained when an acoustic signal was given just before the go-signal. 5. It is concluded that (i) both the RT and the duration of APA can be modified by a translation of the support surface in a functionally appropriate way by updating the internal representation of the actual stance condition within the central nervous system. Both RT and APA are shortened when the body displacement induced by the push or pull movement and platform translation have the same direction; conversely, an inappropriate translation of the feet requires a greater APA and leads to a longer RT; (ii) both APA and RT are modifiable by platform translation for more than half the time between the go-signal and the focal push or pull movement; (iii) an unspecific effect of platform translation on RT can be identified; it may be mediated by a different neuronal substrate.

Lonely traits and concomitant physiological processes: the MacArthur social neuroscience studies.

Loneliness is a complex set of feelings encompassing reactions to unfulfilled intimate and social needs. Although transient for some individuals, loneliness can be a chronic state for others. Prior research has shown that loneliness is a major risk factor for psychological disturbances and for broad-based morbidity and mortality. We examined differences between lonely and socially embedded individuals that might explain differences in health outcomes. Satisfying social relationships were associated with more positive outlooks on life, more secure attachments and interactions with others, more autonomic activation when confronting acute psychological challenges, and more efficient restorative behaviors. Individuals who were chronically lonely were characterized by elevated mean salivary cortisol levels across the course of a day, suggesting more discharges of corticotropin-releasing hormone and elevated activation of the hypothalamic-pituitary-adrenocorticol axis. An experimental manipulation of loneliness further suggested that the way in which people construe their self in relation to others around them has powerful effects on their self concept and, possibly, on their physiology.

Heterogeneous characteristics of imidazoline-induced insulin secretion.

Imidazolines are regarded as a pharmacological group of insulin secretagogues with one uniform mechanism of action, namely closure of ATP-dependent K+ channels (K(ATP) channels) and, in consequence, depolarization of the plasma membrane, Ca2+ influx and stimulation of secretion. This assumption was investigated by measuring insulin secretion from perifused pancreatic islets in response to three imidazoline compounds and comparing the characteristics of secretion with changes in membrane potential and cytosolic Ca2+ concentration [Ca2+]i of single beta-cells. Phentolamine (32 microM) stimulated insulin secretion from perifused mouse islets in the presence of stimulatory (10 mM and 30 mM) and substimulatory (5 mM) glucose concentrations and even in the absence of glucose. Idazoxan in concentrations up to 500 microM was virtually ineffective in the presence of 5 mM glucose. At 10 mM glucose, there was a moderate but significant increase of secretion by idazoxan, 20 microM being nearly as effective as 100 microM. The effect of phentolamine was of slow onset and irreversible in the time frame of the experiments, while the effect of idazoxan was of fast onset and reversible. Alinidine also stimulated secretion in the presence of 10 mM glucose with fast and reversible kinetics, but in contrast to idazoxan, 100 microM was clearly more effective than 20 microM. These heterogeneous characteristics of secretion were reflected by changes of [Ca2+]i: the increase of [Ca2+]i by phentolamine was slow and only partially reversible, whereas idazoxan led to a smaller, but faster and reversible response. The increase of [Ca2+]i by phentolamine and idazoxan was abolished by the Ca2+ channel blocker D 600. Surprisingly, all three compounds depolarized the beta-cell plasma membrane from a resting potential of -71 mV to about -36 mV. Again, the effect of phentolamine was slow and that of idazoxan and alinidine fast. Thus, the characteristics of phentolamine-induced secretion appear to be attributable to the consequences of K(ATP) channel closure. It is unclear, however, why all three test compounds achieved the same degree of depolarization in spite of their known different efficiency to close K(ATP) channels. Apparently, there are additional mechanisms involved in the action of idazoxan and alinidine, which may contribute to the obvious differences in the characteristics of secretion.