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ABSTRACT: Therapy with either angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB) or thiazolidinediones (TZD) is associated with dose-dependent decrements in hematocrit and hemoglobin levels. We aimed to investigate the impact of the coadministration of TZD and ACEI/ARB on hematocrit and hemoglobin values in uncomplicated patients with type 2 diabetes mellitus and normal serum creatinine.Data from patients with type 2 diabetes currently followed, were reviewed and patients treated with ACEI/ARB and/or TZD were identified. For the purpose of this study the following 4 groups of 30 stable non-anemic diabetic patients each matched for age, gender, and BMI were formed. Group ACEI/ARB included patients on ACEI/ARB without TZD, group TZD included patients on TZD and antihypertensive agents other than ACEI/ARB, group ACEI/ARB/TZD consisted of patients on combined therapy with ACEI/ARB and TZD and the control group C included patients never exposed to ACEI/ARB or TZD. Clinical and laboratory data were collected prior to initiation of treatment and after 6 months.Neither hematocrit nor hemoglobin showed any significant change from baseline at the end of the study in group C. In both group ACEI/ARB and group TZD a small, but statistically significant reduction in hematocrit (~ 1% point) and hemoglobin levels (~ 0.3 g/dl) was seen. A greater statistically and clinically important reduction in hematocrit (~ 3% points) and hemoglobin (~ 1 g/dl) levels was observed in group ACEI/ARB/TZD. Furthermore, incident anemia at the end reached 7% in group TZD and 23% in group ACEI/ARB/TZD.Coadministration of RAS inhibitors and PPAR-γ agonists should be considered in the differential diagnosis of hematocrit lowering and anemia in uncomplicated type 2 diabetic patients with normal serum creatinine. Further studies are required to clarify the mechanism(s), the cardiovascular consequences and the cost utility of anemia workup in such patients.
Experimental and Clinical Endocrinology & Diabetes 03/2012; 120(7):416-9. · 1.69 Impact Factor
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ABSTRACT: Background. The aim of this study was to investigate the association of oxytocin with trait and state psychological factors in type 2 diabetic patients. Methods. OXT and psychological variables were analyzed from 86 controlled diabetic patients (glycosylated haemoglobin A1c (HbA1c) < 7%) from 45 uncontrolled diabetic patients (HbA1c ≥ 7). Psychological characteristics were assessed with the Eysenck Personality Questionnaire (EPQ), while state psychological characteristics were measured with the Symptom Checklist 90-R (SCL 90-R). Blood samples were taken for measuring oxytocin in both subgroups during the initial phase of the study. One year later, the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments. Results. During the first evaluation of the uncontrolled diabetic patients, a statistically significant positive relationship between the levels of OXT and psychoticism in EPQ rating scale (P < 0.013) was observed. For controlled diabetic patients, a statistically significant negative relationship between oxytocin and somatization (P < 0.030), as well as obsessive-compulsive scores (P < 0.047) in SCL-90 rating scale, was observed. During the second assessment, the values of OXT decreased when the patients managed to control their metabolic profile. Conclusions. The OXT is in association with psychoticism, somatization, and obsessionality may be implicated in T2DM.
Experimental Diabetes Research 01/2012; 2012:560864. · 1.20 Impact Factor
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ABSTRACT: Although insulin resistance in obesity is established, the link between excess body fat and skeletal muscle insulin resistance is obscure. The aim of this study was to investigate whether cytokines secreted from the subcutaneous adipose tissue are related to the sensitivity of glucose metabolism to insulin in skeletal muscle.
A meal was given to 14 obese and 10 non-obese women. Plasma samples were taken for 360 min from a forearm vein and from the radial artery for glucose and insulin measurements. Interleukin-6, leptin, TNFα, resistin and adiponectin were measured preprandially from the radial artery and from the superficial epigastric vein. Forearm blood flow was measured with plethysmography.
(1) In obese vs non-obese: (a) Glucose uptake by skeletal muscle was decreased (AUC (0-360)369 ± 55 vs. 877 ± 146 μmol/100 g tissue, p=0.001) (b) arterial interleukin-6 (2.5 ± 0.5 vs. 1 ± 0.1 pg/ml, p=0.013) and subcutaneous venous interleukin-6 (5 ± 0.5 vs. 3.4 ± 0.5 pg/ml, p=0.027) were increased (c) arterial leptin (63 ± 7 vs. 5 ± 0.6 ng/ml, p<0.0001) and subcutaneous venous leptin 80 ± 8 vs. 6.5 ± 0.7 ng/ml, p<0.0001) were increased. (2) Arterial interleukin-6 (p=0.002) and subcutaneous venous interleukin-6 (p=0.014) were negatively associated with forearm glucose uptake in obese. (3) No association was found between leptin and forearm glucose uptake, after correcting with fat mass.
In morbid obesity: (1) Subcutaneous adipose tissue releases interleukin-6 which could then mediate insulin resistance in skeletal muscle. (2) Although there is increased secretion of leptin by the subcutaneous adipose tissue, leptin levels are not correlated to the sensitivity of glucose metabolism to insulin in muscle.
Experimental and Clinical Endocrinology & Diabetes 08/2011; 119(8):484-9. · 1.69 Impact Factor
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ABSTRACT: Adiponectin, an adipose tissue secreted protein, exhibits anti-inflammatory and antiatherogenic properties. We examined the effects of the globular and full-length adiponectin on cytokine production in macrophages derived from Coronary Artery Disease (CAD) patients and control individuals. Adiponectin's effects in human macrophages upon lipopolysaccharide (LPS) treatment were also examined. Full length adiponectin acted differently on TNF-α and IL-6 production by upregulating TNF-α and IL-6 protein production, but not their mRNA expression. Additionally, full length adiponectin was unable to abrogate LPS proinflammatory effect in TNF-α and IL-6 mRNA expression in CAD and NON-CAD macrophages. In contrast, globular adiponectin appeared to have proinflammatory properties by potently upregulating TNF-α and IL-6 mRNA and protein secretion in human macrophages while subsequently rendered cells resistant to further proinflammatory stimuli. Moreover, both forms of adiponectin powerfully suppressed scavenger MSR-AI mRNA expression and augmented IL-10 protein release, both occurring independently of the presence of LPS or CAD. These data indicate that adiponectin could potentially protect human macrophages via the elevated IL-10 secretion and the suppression of MSR-AI expression. It can also be protective in CAD patients since the reduced adiponectin-induced IL-6 release in CAD macrophages compared to controls, could be beneficial in the development of inflammation related atherosclerosis.
Hormone and Metabolic Research 05/2011; 43(8):537-44. · 2.19 Impact Factor
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ABSTRACT: Glucagon has been proposed to contribute to the increased glucose production found in hyperthyroidism. However, fasting plasma glucagon levels are not increased in hyperthyroidism suggesting that the activity of the α-cell is normal. Nevertheless, an increase in the clearance rate of glucagon may mask increased glucagon secretion. This study was designed to examine the effects of hyperthyroidism on the kinetics of glucagon.
A primed-continuous infusion of glucagon was administered to 9 euthyroid and 9 hyperthyroid subjects at 3 sequential rates (1,200, 3,000 and 6,000 pg/kg/min, each given for 2 h). Arterialized blood was drawn at 15-30 min intervals for determination of glucagon.
Fasting plasma glucagon levels were comparable in euthyroids (195±8 pg/ml) and hyperthyroids (231±16 pg/ml). During infusions (1,200, 3,000 and 6,000 pg/kg/min), plasma glucagon increased to 387±19, 624±44 and 977±51 pg/ml in euthyroids and to 348±23, 597±42 and 938±56 pg/ml in hyperthyroids respectively. At these infusion rates, metabolic clearance of glucagon (ml/kg/min) was 6.6±0.5, 7.4±0.6 and 7.9±0.5 in euthyroids and 12.6±2, 8.9±1 and 8.8±0.6 in hyperthyroids, respectively. Metabolic clearance of glucagon differed between hyperthyroids and euthyroids at 1 200 pg/kg/min infusion rate (p=0.001). The basal delivery rate of glucagon (ng/kg/min) was 1.3±0.1 in euthyroids and 2.9±0.6 in hyperthyroids (p=0.0005).
In hyperthyroidism, the secretion and metabolic clearance rates of glucagon are increased. These effects may explain the changes in plasma glucagon levels observed in hyperthyroidism and support the important role of glucagon in increasing endogenous glucose production in this condition.
Experimental and Clinical Endocrinology & Diabetes 01/2011; 119(4):214-7. · 1.69 Impact Factor
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ABSTRACT: Adrenal incidentalomas (AIs) represent adrenal masses that are incidentally discovered whilst investigating symptoms and signs unrelated to adrenal pathology. The onset and natural course of AIs are unknown, and the possible underlying cardiometabolic abnormalities have not been examined in depth. A growing body of clinical and experimental evidence supports the notion that both functioning and, paradoxically, nonfunctioning AIs are associated with a partially expressed or even full-blown metabolic syndrome (MS) phenotype, through yet unclear mechanisms. Subtle, subclinical or even profound adrenal hormone excess and an increased proinflammatory state might explain to some extent the development of MS disturbances. The emerging association between AIs and MS appears to be important in determining the optimal clinical management of these patients and raises speculation about the exact mechanisms of this interesting cause-effect relationship.
Journal of Internal Medicine 09/2010; 268(6):555-66. · 5.48 Impact Factor
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P Mitrou,
E Boutati,
V Lambadiari,
E Maratou,
V Komesidou,
A Papakonstantinou,
L Sidossis,
N Tountas,
N Katsilambros,
T Economopoulos, S A Raptis,
G Dimitriadis
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ABSTRACT: Although insulin resistance in obesity is established, information on insulin action on lipid fluxes, in morbid obesity, is limited. This study was undertaken in morbidly obese women to investigate insulin action on triacylglycerol fluxes and lipolysis across adipose tissue.
A meal was given to 26 obese (age 35+/-1 years, body mass index 46+/-1 kg m(-2)) and 11 non-obese women (age 38+/-2 years, body mass index 24+/-1 kg m(-2)). Plasma samples for glucose, insulin, triglycerides and non-esterified fatty acids (NEFAs) were taken for 360 min from a vein draining the abdominal subcutaneous adipose tissue and from the radial artery. Adipose tissue blood flow was measured with (133)Xe.
In obese vs non-obese: (1) Arterial glucose was similar, but insulin was increased (P=0.0001). (2) Adipose tissue blood flow was decreased (P=0.0001). (3) Arterial triglycerides (P=0.0001) and NEFAs (P=0.01) were increased. (4) Lipoprotein lipase was decreased (P=0.0009), although the arteriovenous triglyceride differences were similar. (5) Veno-arterial NEFA differences across the adipose tissue were similar. (6) NEFA fluxes and hormone-sensitive lipase-derived glycerol output from 100 g adipose tissue were not different. (7) Total adipose tissue NEFA release was increased (P=0.02).
In morbid obesity: (a) hypertriglycerinemia could be attributed to a defect in the postprandial dynamic adjustment of triglyceride clearance across the adipose tissue, partly caused by blunted BF; and (b) postprandially, there is an impairment of adipose tissue to buffer NEFA excess, despite hyperinsulinemia.
International journal of obesity (2005) 04/2010; 34(4):770-4. · 4.34 Impact Factor
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Hormone and Metabolic Research 11/2007; 39(10):705-6. · 2.19 Impact Factor
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ABSTRACT: Visfatin, is a new adipokine, highly expressed in the visceral fat of both mice and humans. To examine whether visfatin is expressed in human peripheral monocyte-enriched mononuclear cells and whether its expression is altered in type 2 diabetes (DM2), we compared 24 DM2 women [17 overweight (BMI >25) and 7 lean (BMI<25)] to 26 healthy women (14 overweight and 12 lean), all premenopausal. Relative visfatin mRNA levels were significantly higher (approximately 3-fold) in DM2 compared to healthy control women (p<0.02), independently of the presence of overweight/obesity. Mononuclear TNF-alpha and IL-6 mRNA expression was also elevated in DM2 compared to control women (p=0.001 and p=0.004, respectively), an increase observed in both lean and overweight DM2 women. By contrast, circulating visfatin, TNF-alpha, and IL-6 levels showed no difference between DM2 and control women, while adiponectin plasma levels were significantly decreased in the DM2 women (p<0.001). Circulating visfatin and TNF-alpha levels did not differ either between the lean and the overweight subgroups of DM2 and control women, while IL-6 plasma levels were significantly higher in both overweight subgroups compared to their lean counterparts. In conclusion, visfatin, TNF-alpha, and IL-6 mRNA expressions are increased in peripheral mononuclear-monocytic cells from women with type 2 diabetes, independent of their BMI, which may enhance the effects of their adipose-derived levels and may contribute to the increased insulin resistance and atherogenic risk of these patients.
Hormone and Metabolic Research 10/2007; 39(10):758-63. · 2.19 Impact Factor
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ABSTRACT: In white blood cells (WBC), the increase in glucose utilization is a prominent feature during immune response and this depends on the function of specific glucose transporter (GLUT) isoforms. The objective was to examine the effects of activation by Phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS) and insulin on the expression of GLUT isoforms in all subpopulations of WBC.
Blood was withdrawn from 27 healthy subjects. The expression of GLUT1, GLUT3 and GLUT4 on the plasma membrane of resting and activated monocytes, T- and B-lymphocytes and polymorphonuclear cells (PMNs) was determined in the absence and presence of physiological concentrations of insulin, by flow cytometry.
GLUT1 did not respond to insulin in either resting or PMA/LPS activated state. In the resting state, monocytes and B-lymphocytes increased the abundance of GLUT3 and GLUT4 on their plasma membrane in response to insulin; in contrast, T-lymphocytes and PMNs were unresponsive to insulin. In the activated state, monocytes, B- and T- lymphocytes increased the expression of all three GLUT isoforms on their plasma membrane, whilst PMNs increased only GLUT1 and GLUT3; in all WBC, insulin augmented the expression of GLUT4 and GLUT3 isoforms in addition to the stimulation provided by the PMA or LPS treatment alone.
Activation of WBC leads to increased expression of GLUT1, GLUT3 and GLUT4 isoforms on their plasma membrane; this process was further augmented by insulin. During infection, these mechanisms may help to redistribute glucose as a potential source of energy away from peripheral tissues and direct it towards cells that mediate the immune response and are therefore crucial to survival.
European Journal of Clinical Investigation 05/2007; 37(4):282-90. · 3.02 Impact Factor
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ABSTRACT: The metabolic syndrome (MetS) is a cluster of risk factors related to cardiovascular disease. Prediabetes, identified by impaired fasting glucose and/or impaired glucose tolerance, may predict future development of diabetes mellitus. However, it is not clear whether MetS and prediabetes represent the same or different clinical entities. This study compares MetS and prediabetes in terms of cardiovascular risk factors and target organ damage.
A total of 524 overweight and obese (body mass index, BMI >or= 27 kg/m (2)) adults, mean age 53.6 +/- 10.3 years, 264 men and 260 women, were studied. All participants underwent a thorough clinical and laboratory evaluation, including an oral glucose tolerance test and insulin measurements. Echocardiography, carotid ultrasonography, and pulse wave analysis were also performed for the detection of target organ damage. NCEP-ATP III and ADA criteria were used for the diagnosis of MetS and prediabetes.
The prevalence of MetS and prediabetes was 38.7 and 25.4 %, respectively. Overall, 129 individuals (24.6 %) had MetS without prediabetes (group M) and another 59 (11.3 %) prediabetes without MetS (group P). Group P had decreased albumin excretion (p = 0.033) and more thickened common carotid intima-media in comparison to group M (p = 0.032). Furthermore, group M was associated with higher C-reactive protein levels. Multiple logistic regression analysis revealed that advanced age (p < 0.0001, OR 1.11, 95 % CI 1.06 - 1.16), low insulin secretion (p < 0.0001, OR 0.05, 95 % CI 0.02 - 0.18 for insulinogenic index), and increased insulin resistance (p = 0.0003, OR 3.22, 95 % CI 1.71 - 6.07 for HOMA-IR) were associated with group P.
Our data demonstrate that MetS and prediabetes have an overlapping pattern. MetS appears to have a more pronounced effect on early renal dysfunction and increased inflammatory activation, while prediabetes tends to be associated with early carotid structural changes. These findings may be due to a different pathophysiologic substrate of these clinical phenotypes in terms of insulin resistance and secretion, as well as to the varying prevalence of cardiovascular risk factors.
Experimental and Clinical Endocrinology & Diabetes 07/2006; 114(7):377-83. · 1.69 Impact Factor
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ABSTRACT: The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, while prediabetes, identified by impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), predicts future development of diabetes mellitus. Although MetS and prediabetes have a strong interrelation, it is unclear whether they denote the same risk for cardiovascular complications. The aim of the study was to compare overweight and obese individuals with MetS and prediabetes in terms of early carotid artery atheromatosis and renal dysfunction.
A total of 524 overweight and obese (body mass index, BMI = or >27 kg/m2) adults, mean age 56.7+/-11.8 years, 264 men and 260 women, were studied. All participants underwent a thorough clinical and laboratory evaluation, including an oral glucose tolerance test. Carotid artery ultrasonography was performed and 24 h urine albumin excretion was measured. NCEP-ATP III and ADA criteria were used for the diagnosis of MetS and prediabetes.
Overall, 129 individuals (24.6%) had MetS without prediabetes and another 59 (11.3%) prediabetes without MetS. Individuals with prediabetes had lower albumin excretion (P=0.033) and more thickened common carotid intima-media in comparison to those with MetS (P=0.032). Furthermore, MetS was associated with higher C-reactive protein levels in comparison to prediabetes (P=0.05).
The MetS seems to have a more pronounced impact on early renal dysfunction than prediabetes, while the latter to early carotid artery structural changes.
International angiology: a journal of the International Union of Angiology 07/2006; 25(2):179-83. · 1.65 Impact Factor
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ABSTRACT: Vertebral bone mineral density (BMD) measurements by DXA are considered reliable indicators of local fracture risk in the absence of radiographic deformities. The clinical evaluation of one individual vertebra presenting a BMD value significantly less than the others is attempted in this study. For a period of 30 months, BMD measurements of L1-L4 vertebrae and femoral neck (FN) were performed by DXA in 817 postmenopausal women, aged under 65 years, with a BMI less than 33 kg/m(2). In 204 (25%) of these women (group A), the least dense vertebra (LDV) presented a BMD value lower than 92.4% from the immediate denser vertebra. The remaining 613 women comprised group B. Women with X-ray proven vertebral degenerative lesions or deformities were excluded from the study. Among the four measured vertebrae, L1 was the most frequent LDV (47%), whilst L3 was the most rare (2%). Absolute and age-adjusted BMD values of L1-L4 and FN, as well as the proportions of osteopenic or osteoporotic women, did not differ significantly between the two groups. A significant positive correlation was observed between either L1-L4 or LDV and FN BMD values in both groups, but stepwise multiple regression analysis revealed that in group A the LDV did not participate in the model explaining the variability of the FN BMD values. In group B, the least dense vertebra was the only variable participating in the respective model (adjusted-R(2) = 37.7%). It is concluded that in a significant proportion of relatively young postmenopausal women, a wide variance of BMD values exists between individual vertebral BMD values without radiographic background. L1 was the most frequent LDV and L3 the most rare. In such cases, the evaluation of the least dense vertebra seems to offer an alternative estimation of vertebral bone mass, instead of mean L1-L4.
Maturitas 04/2006; 53(4):476-82. · 2.77 Impact Factor
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C Triantos,
J Vlachogiannakos,
A Armonis,
A Saveriadis,
A Kougioumtzian,
G Leandro,
S Manolakopoulos,
D Tzourmakliotis, S A Raptis,
A K Burroughs,
A Avgerinos
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ABSTRACT: To compare endoscopic banding ligation vs. no treatment in cirrhotics with intolerance or contraindications to beta-blockers for prevention of first bleeding in portal hypertension.
A sample size of 214 was planned with all sizes of varices. However, the trial was stopped due to increased bleeding in 52 patients in the ligation group. The baseline severity liver disease and endoscopic features were similar. Ligation group: 25 (M/F = 21/4, mean age: 60 +/- 9.37 years); 27 not-treated group: 27 (M/F = 17/10, mean age: 63 +/- 10.27).
The mean follow-up period was 19.5 +/- 13.3 months: five bled in the ligation group (20%), three from varices (two after banding at 11 and 17 days; one during the procedure), and two from gastropathy; two bled in the not-treated group (7%- two both varices) (P = 0.24). There were seven deaths in the ligation group and 11 in the not-treated group (P = 0.39).
Sixty per cent of the bleeding in the banding group was probably iatrogenic, requiring the study to be stopped. Endoscopic banding ligation was no better than no treatment. This study suggests that ligation may be harmful when used as primary prophylaxis, similar to prophylactic sclerotherapy in the past.
Alimentary Pharmacology & Therapeutics 07/2005; 21(12):1435-43. · 3.77 Impact Factor
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ABSTRACT: Premature menopause is a known risk factor for osteoporosis, whilst the influence of type 2 diabetes on bone mineral density (BMD) is still controversial.
BMD values assessed by dual-energy X-ray absorptiometry (DXA) in L2-L4 vertebrae and the femoral neck (FN) of 40 diabetic women with premature menopause (D-EMP) were compared with those of 60 non-diabetic, prematurely menopausal women (EMP) and 60 diabetic women with normal menopause (D-NMP) who had been matched by age and body mass index (BMI). In all women, the time elapsed since menopause ranged between 10 and 25 years and the duration of diabetes exceeded 75% of the postmenopausal time period. The age of D-EMP women was 58.7+/-5 years (mean+/-1 s.d.), age at menopause 39.5+/-2.7, years since menopause 18.6+/-4.9, BMI 27.8+/-4.3 kg/m(2) and duration of diabetes 13.9+/-3.9 years.
Vertebral BMD values of D-EMP women were significantly higher than those of EMP women (0.908+/-0.135 vs. 0.817+/-0.14 g/cm(2), P = 0.002), although there was no significant difference between D-EMP and D-NMP women (0.886+/-0.15 g/cm(2)). No significant differences were observed in FN BMD values between all groups. Age-adjusted BMD values (Z scores) of D-EMP women were higher than EMP women in both anatomic sites (P < 0.01), but did not differ from D-NMP women. In contrast to the other two groups, no statistically significant correlation was observed in D-EMP women between the BMD values of either anatomic area and the time elapsed since menopause. HbA(1c) values were positively correlated only to vertebral BMD values of the D-EMP group (P < 0.05). No correlation was observed between the BMD values and the duration of diabetes either in D-EMP or in D-NMP women.
Type 2 diabetes seems to positively affect the mineral density of the trabecular bone in women with premature menopause. The duration of diabetes does not appear to influence bone mass.
European Journal of Endocrinology 03/2005; 152(3):437-42. · 3.42 Impact Factor
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D Pectasides,
M Pectasides,
D Farmakis,
V Kostopoulou,
M Nikolaou,
A Gaglia,
M Koumpou,
N Mylonakis,
N Xiros,
T Economopoulos, S A Raptis
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ABSTRACT: The aim of this study was to evaluate whether docetaxel (taxotere) treatment with or without irinotecan improved patient outcomes with similar toxicity in recurrent non-small-cell lung cancer (NSCLC).
Patients with recurrent platinum-refractory NSCLC with Eastern Cooperative Oncology Group performance status of 0-2 were randomized to either docetaxel 30 mg/m(2) and irinotecan 60 mg/m(2) (days 1 and 8) or docetaxel 75 mg/m(2) (day 1), both administered every 3 weeks.
A total of 130 patients were randomized. The response rate (RR) (20% versus 14%), overall survival (6.5 months versus 6.4 months) and 1-year survival (37% versus 34%) were similar in the combination and docetaxel arms, respectively. The combination arm demonstrated a longer time to tumor progression (TTP) (5.6 versus 4.8 months; P=0.065). Grade 3-4 neutropenia and anemia were similar in the combination and docetaxel arms. Grades 3-4 non-hematological toxicity (except diarrhea) was mild and was similar in the two groups. Grade 3-4 thrombocytopenia (17% versus 6%; P=0.04) and diarrhea (12% versus 3%; P=0.05) occurred more frequently in the combination arm.
The administration of irinotecan with docetaxel in platinum-refractory NSCLC prolonged TTP, but did not improve significantly RR, median survival or 1-year survival. Second-line docetaxel monotherapy offers significant and reproducible efficacy in platinum-refractory NSCLC.
Annals of Oncology 03/2005; 16(2):294-9. · 6.43 Impact Factor
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N Tentolouris,
E Boutati,
N Karambakalis,
D Perrea,
D Perea,
A D Tselepis,
C Tsoukala,
D Kyriaki,
E Lourida,
I Anastasopoulou,
A Karafoullidou, S A Raptis,
N Katsilambros
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ABSTRACT: Postprandial glycaemia and lipaemia are known risk factors for atherosclerosis in type 2 diabetes. Coagulation activation in the postprandial state also contributes to acceleration of atherosclerosis. Nateglinide is effective in reducing postprandial glycaemia. Its effect on glycaemia may also be beneficial in postprandial lipaemia and coagulation. The aim of this study was to examine the potential effect of a single dose of nateglinide on postprandial triglyceridaemia, coagulation, and fibrinolysis in patients with type 2 diabetes.
Ten subjects with type 2 diabetes, treated with diet alone were recruited in a crossover randomized study. In the morning, after a 12- to 14-h fast, each subject received a standard mixed meal (total energy 783 kcal), preceded by one tablet of 120 mg nateglinide or placebo. Venous blood samples were drawn prior to meal consumption and 6h afterwards for the measurement of plasma glucose, insulin, and C-peptide, lipids, coagulation, and fibrinolysis factors. As expected, there was a significant reduction in postprandial glycaemia after nateglinide administration compared to placebo (P<0.001). Plasma insulin levels were significantly higher after nateglinide than after placebo (P=0.002). Nateglinide administration resulted in a lower overall postprandial reduction of tissue-plasminogen activator than placebo (-2.9+/-1.3 vs. -8.3+/-3.7 ng/ml h, P=0.003). In addition, a significant reduction of postprandial plasminogen activator inhibitor-1 was observed in comparison with the baseline values after nateglinide (P=0.001), although the overall response was not significantly different after nateglinide and placebo (P=0.31). Plasma concentrations of C-peptide, lipids and the remaining coagulation parameters studied were not different between nateglinide and placebo.
Acute nateglinide administration improves postprandial glycaemia and fibrinolytic activity in patients with type 2 diabetes. This combined effect, if confirmed by a long-treatment study, might reduce cardiovascular risk in type 2 diabetes.
Nutrition Metabolism and Cardiovascular Diseases 02/2005; 15(1):6-12. · 3.73 Impact Factor
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ABSTRACT: In hyperthyroidism, tissue glucose disposal is increased to adapt to high energy demand. Our aim was to examine the glucose transporter isoforms involved in this process and their regulation through insulin in monocytes from subjects with hyperthyroidism.
Blood (20 ml) was withdrawn from 12 healthy and 12 hyperthyroid subjects. The abundance of glucose transporter isoforms (GLUT) on the monocyte surface membrane was determined in the absence and presence of insulin (10-100 mU/l) using flow cytometry. Anti-CD14-PE monoclonal antibody was used for monocyte gating. GLUT isoforms were determined after staining the cells with specific antisera to GLUT1, GLUT3 and GLUT4.
Hyperthyroidism increased basal monocyte-surface GLUT1, GLUT3 and GLUT4 transporters. In these cells, insulin had a marginal effect on GLUT4 translocation (25 %, p < 0.02) and a more significant effect on GLUT3 translocation (45 %, p < 0.001) on plasma membrane.
In the hyperthyroid state, (1) basal abundance of GLUT1, GLUT3 and GLUT4 transporters on the cell surface is increased; (2) insulin mainly increases the recruitment of GLUT3 and, to a lesser extent, GLUT4 glucose transporters on the plasma membrane. These findings may provide a mechanism to explain the increment of glucose disposal in peripheral tissues in hyperthyroidism.
Hormone and Metabolic Research 02/2005; 37(1):15-20. · 2.19 Impact Factor
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ABSTRACT: Many factors, such as oxygen and vasculature, are involved in the cytotoxic effect of photodynamic therapy (PDT). It is known that somatostatin and its analog octreotide decrease the splanchnic blood flow and have multiple inhibitory effects in different functions of the peptic system. The aim of this experimental study was to assess the effect of octreotide administration on PDT outcome in normal pig stomach.
28 healthy pigs, randomly assigned to two groups, A and B, were studied. Pigs in both groups were sensitized with 0.3 mg/kg intravenous meta-tetra (hydroxyphenyl) chlorin (m-THPC), and 48 hours later light of wavelength 650 nm was delivered from a 50-mW diode laser for 300 s (energy fluence 15 J/cm (2)) through a gastroscope to the gastric mucosa. Group A underwent PDT without octreotide and group B had PDT with administration of octreotide. At 72 h after light delivery, all the animals were sacrificed for macroscopic and histological evaluation of the irradiated site.
The macroscopic images and the histology of the stomach PDT lesions (inflammation, ulceration, necrosis) showed significantly less severity in the group of animals with octreotide injection (group B). In this group, full-thickness necrosis was observed in 28.5 %, compared with over 71.4 % in group A; this was statistically significant ( P < 0.05).
Octreotide may have a modulating effect on m-TPHC PDT in normal gastric tissue in pigs, probably due to alterations of hemodynamics in the stomach and to suppression of the inflammatory process.
Endoscopy 10/2004; 36(10):893-7. · 5.21 Impact Factor
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ABSTRACT: In type 2 diabetes (T2D) insulin secretion after a meal is delayed; this may have an impact on the development of hyperglycaemia and hyperlipidaemia.
To investigate this, a meal was given to 15 T2D (age 52 +/- 2 years, BMI 25 +/- 0.8 kg m(-2)) on three different occasions: (1) without treatment, (2) after 120 mg of nateglinide before the meal (acute treatment), and (3) after 3 months of nateglinide (120 mg t.i.d., chronic treatment). Fifteen healthy subjects (CON, age 48 +/- 2 years, BMI 24 +/- 0.5 kg m(-2)) were also studied. Blood was withdrawn for 360 min from veins draining the anterior abdominal subcutaneous adipose tissue (AD) and from an arterialized hand vein. Blood flow (BF) in AD was measured with (133)Xe. Lipoprotein lipase activity (LPL) was calculated as the triacylglycerol (TAG) flux across AD, and hormone-sensitive lipase (HSL) as the glycerol flux minus LPL.
(1) In T2D the increase in prandial insulin secretion was delayed; postprandial nonesterified fatty acid (NEFA) and TAG levels in blood were increased, while BF, LPL and TAG clearance were blunted vs. CON. (2) Acute or chronic nateglinide treatment induced a prompt increase in prandial insulin secretion, resulting in a decrease in blood glucose and NEFA levels owing to suppression of HSL, while BF, LPL and TAG clearance remained suppressed.
In T2D, restoration of early phase insulin secretion improved postprandial hyperglycaemia and suppressed endogenous lipolysis, resulting in suppression of NEFA levels. These results suggest that in nonobese T2D, metabolic defects may result, to a large extent, from the delay in prandial insulin secretion.
European Journal of Clinical Investigation 08/2004; 34(7):490-7. · 3.02 Impact Factor
