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Effect of troglitazone on body fat distribution in type 2 diabetic patients.   总被引:13,自引:0,他引:13  
OBJECTIVE: Troglitazone was recently reported to specifically promote the differentiation of pre-adipocytes into adipocytes in vitro in subcutaneous fat only, indicating a relation to insulin-resistance-improving action of troglitazone. To expand on this finding, we investigated at the clinical level how long-term administration of troglitazone influences the body fat distribution in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Troglitazone (400 mg/day) was administered for 6 months to 30 type 2 diabetic patients whose glycemic control was poor. A total of 18 patients received diet therapy alone (in the single-treatment group, BMI 26.0 +/- 4.6, HbA1c 8.2 +/- 1.7%), and 12 patients concomitantly received glibenclamide (1.25-7.5 mg/day) (in the concomitant sulfonylurea group, BMI 25.4 +/- 4.7, HbA1c 9.2 +/- 1.2%). BMI, HbA1c, serum lipid level, and body fat distribution, which were determined by computed tomography (CT) scan at the umbilical level, were measured and compared before and after troglitazone treatment. RESULTS: During the 6-month troglitazone treatment, HbA1c levels decreased and BMI increased in both groups. As for body fat distribution in the single-treatment group, visceral fat area (VFA) decreased (from 118.3 +/- 54.3 to 101.1 +/- 50.8 cm2; P < 0.001), and subcutaneous fat area (SFA) increased (from 189.7 +/- 93.3 to 221.6 +/- 101.6 cm2; P < 0.001), resulting in a decrease in visceral/subcutaneous (V/S) ratio (from 0.74 +/- 0.48 to 0.50 +/- 0.32; P < 0.001). In the concomitant sulfonylurea group, VFA was unchanged (from 108.1 +/- 53.5 to 112.5 +/- 59.9 cm2), while SFA increased (from 144.6 +/- 122.0 to 180.5 +/- 143.5 cm2; P < 0.01), thereby decreasing the V/S ratio (from 0.91 +/- 0.46 to 0.77 +/- 0.44; P < 0.01). The serum triglyceride level and the area under glucose curve during the 75-g oral glucose tolerance test decreased significantly in the single-treatment group. CONCLUSIONS: According to our data, troglitazone appears to promote fat accumulation in the subcutaneous adipose tissue rather than in the visceral adipose tissue in mildly obese Japanese people with type 2 diabetes. This shift of energy accumulation from the visceral to subcutaneous adipose tissue may greatly contribute to the troglitazone-mediated amelioration of insulin resistance.  相似文献   

3.
ObjectivesTo evaluate oxidative stress and the extent of oxidation of plasma proteins in type 2 diabetic patients.Design and methodsStudy was carried out on blood from 31 diabetic patients of both sexes (mean age = 58 ± 7; duration of diabetes 12 ± 5 years) and healthy age and sex matched normal subjects. Biomarkers of protein oxidation; plasma protein carbonyls (PCO), advanced oxidation protein products (AOPPs) and –SH group and free radical scavenging capacity of plasma was measured.ResultsPCO and AOPPS levels were significantly (P < 0.005) higher in diabetic patients in comparison to healthy volunteers. Reduced free radical scavenging capacity (P < 0.001) and –SH group (P < 0.05) was observed in plasma of type 2 diabetic patients.ConclusionsOur data suggest that diabetics are susceptible to protein oxidation. Oxidative modulation of proteins due to reduced radical scavenging activity of plasma patients may be one of the reasons of altered physiological processes in type 2 diabetic patients.  相似文献   

4.
This cross-sectional study was aimed at investigating the association between eating behaviour and current glycaemic control, body mass or autonomic nervous function in patients with type I and type II diabetes mellitus (DM). In 72 patients (31 type I DM, 41 type II DM) we investigated body mass index (BMI), serum cholesterol, serum triglycerides, haemoglobin A1c (HbA1c) and autonomic nervous function (seven standardized tests). The three-factor eating questionnaire was used to investigate cognitive control of eating behaviour (CC) and susceptibility to eating problems (SEP). The mathematical product of CC and SEP provides information about disinhibition of eating control (DEC). In type I DM, there was a correlation between SEP and age ( r =−0.536, P <0.01), SEP and duration (−0.441, P <0.05), SEP and HbA1c (0.438, P <0.05), and between DEC and duration (−0.371, P <0.05) and DEC and HbA1c (0.376, P <0.05). In type II DM, there was a correlation between SEP and BMI (0.401, P <0.01) and between DEC and BMI (0.429, P <0.01). Low CC was associated with autonomic nervous dysfunction in type I DM ( P =0.022). In type II DM, autonomic nervous dysfunction was associated with high SEP ( P =0.044). In conclusion, the correlation between eating behaviour and HbA1c or triglycerides in type I DM indicates that the questionnaire is able to address current parameters of diabetes control. Self-assessment of eating behaviour in type I and type II diabetic patients reveals associations between eating behaviour and autonomic nervous function.  相似文献   

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OBJECTIVE--This study was designed to examine metabolic and hormonal effects of long-term exercise in healthy subjects and insulin-dependent (type I) diabetic patients. RESEARCH DESIGN AND METHODS--Two studies were performed. First, 16 healthy males (32 +/- 3 yr) were studied during a semitriathlon competition (2 km swimming, 90 km biking, and 21 km running). Second, 9 type I diabetic males (41 +/- 2 yr) and 17 healthy matched control subjects were studied during a 75 km cross-country skiing race. Blood samples were taken before and immediately after exercise, and also during the ski race. RESULTS--During the semitriathlon race, serum insulin, C-peptide, glucagon cortisol, growth hormone ACTH, prolactin, and plasma renin activity increased two- to ninefold, whereas serum testosterone fell. Apart from a fall in magnesium, serum electrolyte concentrations remained unchanged. Before long-term skiing, patients reduced their insulin dose by 30-40%. They were hyperglycemic during the initial part of the race, but near normoglycemic thereafter. There were large interindividual variations in the increments of counterregulatory hormones, whereas serum testosterone and luteinizing hormone fell quite uniformly. Plasma renin activity and aldosterone concentrations rose similarly in diabetic and healthy subjects, whereas the rise in antidiuretic hormone was slightly greater in diabetic patients. During the initial part of the race, serum atrial natriuretic peptide fell in both groups. CONCLUSIONS--Severalfold increments in hormone concentrations contribute to the maintenance of fuel and fluid homeostasis during long-term exercise. With an appropriate adjustment of insulin dose and diet, also type I diabetic patients can participate in competitive long-term exercise.  相似文献   

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Systolic and diastolic left ventricular function was assessed by M-mode and pulsed Doppler echocardiography in 10 young type I diabetic patients without late complications and maximal diabetes duration of 5 years and in 10 healthy persons. Fractional shortening, a measure of systolic ventricular function, was significantly lower in diabetics than in controls (33.9 +/- 2.9 vs. 37.9 +/- 4.9; p less than 0.05). Fractional shortening decreased significantly with advancing diabetes duration (R = -0.819; p less than 0.01). Indexes of diastolic ventricular function (isovolumetric relaxation period and transmitral flow velocity pattern) were not significantly different in the two groups, but 3 patients had 1 parameter (3x isovolumetric relaxation period) and another patient had 2 parameters (isovolumetric relaxation period and early diastolic peak velocity E-E') outside the normal range. Follow-up studies should define the clinical significance of these alterations of systolic and diastolic left ventricular function.  相似文献   

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1. To examine whether insulin resistance in uraemia extends to amino acid metabolism, the effect of physiological hyperinsulinaemia on plasma amino acid concentrations was studied in 17 chronically uraemic and 28 healthy subjects by using the euglycaemic insulin clamp technique. 2. In six uraemic and seven control subjects, splanchnic and leg exchange of amino acids was quantified with hepatic and femoral venous catheterization, and in five uraemic and eight control subjects intracellular free amino acid concentrations were determined in muscle tissue obtained by needle biopsy. 3. In response to hyperinsulinaemia the plasma concentrations of all amino acids except alanine decreased by 10-50% in both uraemic and control subjects. Splanchnic alanine uptake declined by 20% and leg amino acid release tended to decrease in both groups. 4. The intracellular levels of all measured amino acids except alanine fell significantly and to a similar extent in uraemic and control subjects. 5. These results indicate that insulin-mediated alterations in regional amino acid exchange and in plasma and intracellular amino acid concentrations are similar in uraemic and control subjects. 6. It is concluded that tissue insensitivity to insulin in uraemia does not extend to uptake or release of amino acids and that resistance to insulin can be selective in its effect on different metabolic functions.  相似文献   

8.
The inter-organ flux of substrates after a protein-rich meal was studied in seven healthy subjects and in eight patients, with diabetes mellitus. Arterial concentrations as well as leg and splanchnic exchange of amino acids, carbohydrate substrates, free fatty acids (FFA), and ketone bodies were examined in the basal state and for 3 h after the ingestion of lean beef (3 g/kg body wt). Insulin was withheld for 24 h before the study in the diabetic patients. In the normal subjects, after protein ingestion, there was a large amino acid release from the splanchnic bed predominantly involving the branched chain amino acids. Valine, isoleucine, and leucine accounted together for more than half of total splanchnic amino acid output. Large increments were seen in the arterial concentrations of the branched chain amino acids (100-200%) and to a smaller extent for other amino acids. Leg exchange of most amino acids reverted from a basal net outut to a net uptake after protein feeding which was most marked for the branched chain amino acids. The latter accounted for more than half of total peripheral amino acid uptake...  相似文献   

9.
OBJECTIVE: To assess the frequency and possible risk indicators of severe hypoglycemia in insulin-dependent (type I) diabetic patients with impaired kidney function. RESEARCH DESIGN AND METHODS: Retrospective follow-up examination of case subjects and control subjects with mean follow-up periods of 2.9 and 1.3 yr, respectively. The setting was the diabetes center at the Düsseldorf University hospital. Subjects were consecutive type I diabetic patients. Case subjects consisted of 44 patients with initial serum creatinine levels of greater than or equal to 133 microM and pathological proteinuria. Control subjects consisted of 46 patients with normal serum creatinine levels matched for age, duration of diabetes, and hypertension; 57% of case subjects and 67% of control subjects were being treated with beta-blockers. Incidence of severe hypoglycemia (cases/patient-yr) was assessed through an interviewer-administered questionnaire. RESULTS: At comparable levels of HbA1c (7.9 +/- 1.8 vs. 7.6 +/- 1.1%), case subjects had a fivefold higher incidence of severe hypoglycemic episodes (1.28 vs. 0.25 cases/patient-yr, P less than 0.02) than control subjects. Within the group with impaired kidney function, patients with severe hypoglycemic episodes had lower HbA1c levels (7.4 +/- 1.6 vs. 8.7 +/- 2.0%, P less than 0.03) and a lower body mass index (22.0 +/- 3.4 vs. 24.4 +/- 3.8 kg/m2, P less than 0.04) than those without severe hypoglycemic episodes, whereas serum creatinine levels, body weight-related insulin dosage (U x kg-1 x day-1), prevalence of blindness, autonomic neuropathy, and treatment with beta-blockers were comparable. CONCLUSIONS: Type I diabetic patients with impaired kidney function are at an excessively high risk of severe hypoglycemia. In addition to low HbA1c levels, a low body mass index appears to be a risk indicator for this adverse effect of insulin therapy.  相似文献   

10.
Intranasal glucagon can raise blood glucose levels in healthy subjects. The aims of this study were to 1) compare the hyperglycemic effect of intranasal and intramuscular glucagon in healthy subjects and type I (insulin-dependent) diabetes patients during euglycemic conditions and 2) test the efficacy of intranasal and intramuscular glucagon in counteracting hypoglycemic episodes in insulin-treated diabetic patients. Intranasal glucagon raised blood glucose levels in both healthy subjects and type I diabetic patients, the effect of intramuscular glucagon being similar for the first 30 min and higher thereafter. Intranasal glucagon was also quicker acting than oral glucose in healthy subjects. Intranasal glucagon raised blood glucose levels in patients with hypoglycemic episodes, although less effectively than intramuscular glucagon. These data indicate intranasal glucagon as a possible emergency remedy for self-medication in insulin-treated patients prone to hypoglycemic episodes.  相似文献   

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Summary. Surgical trauma is accompanied by increased energy expenditure and raised arterial concentrations of adrenaline and glucose. In order to study the acute effects of an adrenaline infusion on glucose metabolism and oxygen uptake in the leg and splanchnic bed, adrenaline was administered at a rate giving plasma concentrations of adrenaline similar to those in connection with abdominal surgery. Seven healthy males participated in the study. Adrenaline 40 ng/(min×kg body weight) (0·22 nmol/(min×kg body weight)) was infused producing a plasma concentration of 2–77±0·42 nmol/1 (mean±SEM). Leg and splanchnic blood flows and the femoral and hepatic arterio-venous differences for oxygen, glucose, lactate and other metabolites were determined. Measurements were made before and between 30 and 40 min after the start of the adrenaline infusion. Following the infusion of adrenaline the leg blood flow increased by 140% and hepatic blood flow by 25%. The leg oxygen uptake increased by 30%, but no significant increase in splanchnic oxygen uptake was observed. The arterial glucose concentration rose by 35%. Splanchnic glucose output increased × 2·5, but no significant increase in leg glucose uptake was observed. Leg release of gluconeogenic substrates increased but only lactate and glycerol uptake increased in the splanchnic bed. Leg blood flow increased more than that usually seen after surgery, whereas leg oxygen uptake and splanchnic oxygen uptake was higher in the immediate postoperative period. Splanchnic glucose release increased more during the infusion than in connection with surgery. It is concluded that adrenaline at a plasma concentration similar to that during and immediately after surgery can induce changes in glucose metabolism which are of the same order or more pronounced than those seen in connection with abdominal surgery.  相似文献   

13.
OBJECTIVE: To determine the importance of color discrimination ability regarding accuracy in the self-monitoring of blood glucose. RESEARCH DESIGN AND METHODS: Two hundred two insulin-dependent (type I) diabetic patients performed the Fansworth-Munsell 100-hue test and a second group of 159 type I diabetic patients performed a new Düsseldorf 26-hue test. Error scores in both tests were compared with error scores of patients' self-monitoring of blood glucose measurements with Chemstrip Haemoglucotest 20-800 strips. RESULTS: Color discrimination ability decreased with age, diabetes duration, and presence of retinopathy. It was independent of the degree of glycemia and accuracy of self-monitoring of blood glucose. CONCLUSIONS: Impaired color vision by itself is no reason to abandon self-monitoring of blood glucose with visually read strips.  相似文献   

14.
The [125I]fibrinogen uptake test was modified to give a quick result, and improve sensitivity and specificity in the diagnosis of deep venous thrombosis (DVT). At least 800 counts were recorded at each measuring point. The leg veins were emptied more effectively. Thus the proximal thigh could be evaluated and the influence of varicose veins reduced. The feet and the leg points were measured in a zig-zag order (from side to side) to avoid systematic errors in early diagnosis. The modified test detected 62% of the thrombi 1 h after injection, 82% after 1 day and 95% after 2 days. The method still lacks in specificity; this is unavoidable since fibrin accumulates in various other conditions than DVT. The combination of high sensitivity and low specificity makes the modified test reliable as a screening procedure, but not as an independent method.  相似文献   

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The concentrations of tinidazole in various tissues and body fluids were studied in gynaecological patients after a single 2g oral dose. Tinidazole was determined by the agar-diffusion technique using a strain of Clostridium bifermentans. Reliable estimates of concentrations down to 0.5 microng/ml could be obtained. Dichloromethane extraction of tinidazole added to various tissues in known amounts gave a recovery of 100 +/- 10%. Peak serum values of 32-52 microng/ml were reached 3-6h after the administration. The concentrations in peritoneal fluid, obtained at operation 8.5-15h after the intake, varied between 16 and 40 microng/ml. Specimens from the Fallopian tubes yielded 15-26 microng tinidazole/g tissue; similar levels were obtained specimens from myometrium, endometrium, portio, vaginal secretions, omental fat, and cutis. It is concluded that, with the given dose, tinidazole concentrations are achieved in fluids and tissues of the female genital tract that are far in excess of those that should be therapeutical in infections caused by microorganisms know to respond to nitroimidazole treatment.  相似文献   

16.
OBJECTIVE--The aim of this study was to investigate whether a 45-min moderate exercise, performed postprandially with a timing that partially prevented the risk of hypoglycemia, was able to modify platelet function in patients affected by insulin-dependent (type I) diabetes mellitus without severe late complications and in a good metabolic control. RESEARCH DESIGN AND METHODS--We submitted 6 male type I diabetic patients (27.2 +/- 3.4 yr; body mass index, 21.4 +/- 0.6 kg/m2; HbA1c, 7.6 +/- 0.9%) on a daily three-insulin injection regimen, without severe late complications of diabetes, to a 45-min moderate exercise (about 50% of maximal oxygen consumption) with a cycle ergometer, beginning 180 min after breakfast and 195 min after a subcutaneous shot of regular insulin. Serial venous blood samples were conducted to measure plasma glucose, free insulin, counterregulatory hormones (glucagon, growth hormone, cortisol, and catecholamines), platelet sensitivity to ADP, platelet activating factor and collagen, and plasma concentrations of the platelet-specific protein beta-thromboglobulin (a marker of the platelet release reaction in vivo). RESULTS--Exercise was accompanied by a decrease of plasma glucose (from 5.9 +/- 1.2 to 4.6 +/- 1 mmol/L, P = 0.067) and free insulin (from 180 +/- 36 to 114 +/- 30 pmol/L, P = 0.003), and by a significant increase of growth hormone (from 5 +/- 1 to 15 +/- 4 micrograms/L, P = 0.045), cortisol (from 240 +/- 30 to 406 +/- 69 nmol/L, P = 0.018), epinephrine (from 1005 +/- 240 to 5143 +/- 1753 pmol/L, P = 0.077), and norepinephrine (from 5.04 +/- 1.08 to 13.48 +/- 2.98 nmol/L, P = 0.009). Platelet sensitivity to the agonists and plasma concentrations of beta-thromboglobulin increased during the exercise period. In particular, ADP ED50 reached during exercise 61 +/- 16% of basal values (P = 0.048), platelet activating factor ED50 reached 73 +/- 11% (P = 0.043), and collagen ED50 reached 68 +/- 9% (P = 0.008). beta-Thromboglobulin rose from 24 +/- 2 to 32 +/- 3 micrograms/L (P = 0.007). CONCLUSIONS--Moderate exercise enhances platelet function in type I diabetic patients without severe angiopathy and in a good metabolic control.  相似文献   

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Seventy-six type I diabetic patients free of peripheral artery disease and 82 age-matched healthy volunteers were studied by means of transcutaneous oxygen pressure measurements. Two transcutaneous probes were attached to the skin at the subclavian region and at the supramalleolar region. Basal transcutaneous oxygen pressure values and values during breathing of 5 and 10 1 O2 min-1, the rate of rise of oxygen pressure and the time required from the beginning of the oxygen pressure increase to the achievement of its maximum were recorded, and a regional perfusion index was calculated. Nearly all the measured transcutaneous oxygen parameters showed significant differences between diabetic and control subjects. The differences were most pronounced with the transcutaneous oxygen pressure values during oxygen breathing. Even patients with a diabetes duration of less than 1 year and free of any detectable microangiopathic complication, differed significantly from control subjects. These findings may indicate a microcirculatory disturbance in diabetic patients, which might be considered as the manifestation of a functional diabetic microangiopathy preceding any morphological alterations of the vasculature in diabetes mellitus.  相似文献   

18.
OBJECTIVE--To clarify whether the circulating insulin level influences hormonal responses, glucagon secretion in particular, during hypoglycemia in patients with insulin-dependent (type I) diabetes. RESEARCH DESIGN AND METHODS--Nine type I diabetic patients were studied. During two separate experiments, hypoglycemia was induced by low-dose (244 pmol.kg-1.h-1) and high-dose (1034 pmol.kg-1.h-1) intravenous insulin infusions for 180 min in each case. The arterial blood glucose level was directly monitored every 1.5 min, and glucose was infused in the high-dose test to clamp the arterial blood glucose level to be identical as in the low-dose test. RESULTS--Despite the fact that the plasma insulin level was four times higher in the high-dose than in the low-dose test (740 +/- 50 vs. 180 +/- 14 pM), a close to identical arterial hypoglycemia of approximately 3.3 mM was obtained in the two experiments. During hypoglycemia, a significant rise of the plasma glucagon level was found only in the low-dose test (188 +/- 29 vs. 237 +/- 37 ng/L, P less than 0.05), and the incremental area under the glucagon curve was significantly greater in the low-dose than in the high-dose test (140 +/- 19 vs. -22.7 +/- 34 ng/L.h-1, P less than 0.005). The responses of plasma epinephrine, norepinephrine, growth hormone, pancreatic polypeptide, and somatostatin were similar in both tests and, consequently, were not significantly modified by the circulating insulin level. CONCLUSIONS--This study demonstrates that, in type I diabetic patients, the glucagon response to hypoglycemia is suppressed by a high level of circulating insulin within the physiological range. Our findings may help to explain the impairment of glucagon secretion during hypoglycemia frequently seen in these patients.  相似文献   

19.
OBJECTIVE: To evaluate the influence of subcutaneous and intraperitoneal (i.p.) insulin on plasma lipoproteins in type I diabetic (IDDM) patients with end-stage renal failure (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: A before-after trial. SETTING: University hospital outpatient care. PARTICIPANTS: Eleven IDDM patients with stabilized peritoneal dialysis, age 42.9 +/- 2.9 (SEM) years and duration of diabetes 31.4 +/- 3.4 years. INTERVENTION: Two treatment periods during stabilized CAPD. All patients were first treated with subcutaneous and then with i.p. insulin.The studies were performed after a median time of 3 months on each treatment. MAIN OUTCOME MEASURES: Plasma lipids; apoproteins (Apo) A-I, A-II, and B; high-density lipoprotein (HDL) subfractions; glycemic status; and uremic status. RESULTS: After changing from subcutaneous insulin to i.p. insulin, plasma HDL cholesterol decreased (from 1.29 +/- 0.13 mmol/L to 0.96 +/- 0.06 mmol/L, p < 0.05), and the low density to high density lipoprotein (LDL/HDL) cholesterol ratio increased (p < 0.05). The HDL cholesterol decreased in both HDL2 and HDL3 fractions, but significantly so only in HDL3 (p < 0.01). ApoA-I (p < 0.05) decreased while the ApoB/ApoA-I ratio (p < 0.01) and the ApoA-I/HDL-cholesterol ratio (p < 0.01) increased during i.p. insulin therapy. Intraperitoneal insulin resulted in significantly better glycemic control than subcutaneous insulin (p < 0.01). CONCLUSIONS: In diabetic patients on CAPD therapy, i.p. insulin, although inducing better glycemic control than subcutaneous insulin, was associated with lowered plasma HDL cholesterol and ApoA-I levels. The atherogenic potential is probably less than expected as the relative particle size of HDL remained unchanged.  相似文献   

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目的探索和推行更加完善的个体化糖尿病饮食治疗方案。方法选取内分泌科住院中老年超重的2型糖尿病患者60人,按单纯随机抽样法分为对照组和干预组。对照组入院时给予饮食指导,住院期间患者自主安排饮食。干预组患者除入院时饮食指导外,住院期间营养医师据病情需求适时调整每日膳食。结果干预前后比较,干预组各项指标降幅均大于对照组,其中干预组空腹血糖值(FPG)、餐后2 h血糖值(2hPG)、三餐后最大血糖波动值(MFBG,三餐后血糖最高值与最低值之差)、总胆固醇(TC)、三酰甘油(TG)、体质量指数(BMI)下降差异有统计学意义,对照组仅2 hPG、TG指标下降差异有统计学意义。干预后组间比较,FPG、2 hPG、MFBG差异有统计学意义。结论全程个体化饮食治疗有助改善住院2型糖尿病患者代谢指标。  相似文献   

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