Diurnal Glucose Patterns of Exenatide Once Weekly: A 1-Year Study Using Continuous Glucose Monitoring with Ambulatory Glucose Profile Analysis

ObjectiveTo use continuous glucose monitoring (CGM) to characterize diurnal glucose patterns produced by a novel formulation of exenatide consisting of biodegradable polymeric microspheres that entrap exenatide and provide extended release enabling once-weekly administration.MethodsWe performed a subgroup analysis of patients with type 2 diabetes who participated in a multicenter trial (DURATION-1: Effects of Exenatide Long- Acting Release on Glucose Control and Safety in Subjects With Type 2 Diabetes Mellitus) comparing once-weekly with twice-daily formulations of exenatide. We are the only center to use CGM with ambulatory glucose profile (AGP) analysis to characterize glucose exposure, variability, and stability in participants assigned to exenatide once weekly.ResultsSeven of the 303 patients in the larger study population were included in the subgroup analysis. Mean age (57.6 ± 7 years), weight (102 ± 17 kg), body mass index (34 ± 3 kg/m²), and duration of diabetes (5 ± 2 years) were comparable to characteristics of the larger study population. At 30 weeks and 52 weeks, participants treated with exenatide once weekly had a mean reduction in hemoglobin A_1c level of 1.3 ± 0.3% and 1.0 ± 0.3%, respectively (P < .05). CGM analysis revealed a significant (P < .01) decrease in diurnal glucose exposure for 4 participants during nocturnal and daytime periods. Excess glucose exposure (compared with reference values) decreased in 6 of 7 participants, as did glucose variability. Glucose stability improved in 5 participants. The percentage of glucose values less than 70 mg/dL initially increased during the first half of the study then decreased to baseline levels by study end.ConclusionsIndividual glucose profiles revealed that changes in hemoglobin A_1c did not consistently parallel alterations in glucose exposure, variability, and stability. AGPs provided a visual representation of improved glucose responses to exenatide once weekly. (Endocr Pract. 2009;15:326-334)     

Exenatide Therapy in Obese Patients With Type 2 Diabetes Mellitus Treated with Insulin

ObjectiveTo evaluate the effect of exenatide on clinical parameters in obese patients with type 2 diabetes mellitus whose hyperglycemia is not adequately controlled despite treatment with oral hypoglycemic agents and insulin.MethodsIn this retrospective analysis, clinical progress of 52 obese patients with type 2 diabetes treated with exenatide, 5 mcg twice daily, in an outpatient setting was reviewed. Treatment initiation was between September and December 2005. Mean follow-up period was 26 weeks. Thirty-eight patients took exenatide regularly (Group A); 14 patients discontinued exenatide because of insurance, personal, or economic reasons (Group B). Measurements at baseline and at follow-up included body weight; blood pressure; and levels of hemoglobin A_1c (HbA_1c), high-sensitivity C-reactive protein (CRP), and plasma lipids. Insulin dosage requirements were assessed.ResultsMean body weight (± standard error of the mean) decreased by 6.46 ± 0.8 kg (P < .001) in Group A and increased by 2.4 ± 0.6 kg in Group B (P < .001). In Group A, mean HbA_1c decreased by 0.6 ± 0.21% (P = .007), and the insulin dosage requirement decreased for rapid-acting and mixed insulins (P < .02). In Group A, means of the following parameters decreased: serum total cholesterol by 8.5 ± 3.3% (P = .03), triglycerides by 26 ± 7.6% (P = .01), systolic blood pressure by 9.2 ± 3.3 mm Hg (P = .02), and high-sensitivity CRP by 34 ± 14.3% (P = .05). These indices did not change in Group B.ConclusionExenatide effectively treats obese patients with type 2 diabetes on insulin, leading to weight loss and reduction in levels of HbA_lc, systolic blood pressure, triglycerides, and high-sensitivity CRP. (Endocr Pract 2007;13:444-450)     

Glycolipid ester-type heterodimers from Ipomoea tyrianthina and their pharmacological activity

Tyrianthins A (1) and B (2), two new partially acylated glycolipid ester-type heterodimers were isolated from Ipomoea tyrianthina. Scammonic acid A was determined as the glycosidic acid in both monomeric units. Tyrianthin A (1) (IC₅₀ 0.24 ± 0.09 μM and E_max 81.80 ± 0.98%), and tyrianthin B (2) (IC₅₀ 0.14 ± 0.08 μM and E_max 87.68 ± 0.72%) showed significant in vitro relaxant effect on aortic rat rings, in endothelium- and concentration-dependent manners. Also, these compounds were able to increase the release of GABA and glutamic acid in brain cortex, and displayed weak antimycobacterial activity.     

Determination of mildronate by LC–MS/MS and its application to a pharmacokinetic study in healthy Chinese volunteers

A simple, rapid and accurate liquid chromatography–tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the determination of mildronate in human plasma. Following a simple protein precipitation with methanol, the analyte was separated on a C₁₈ column by isocratic elution with methanol and 10 mM ammonium acetate (55:45; v/v), and then analyzed by mass spectrometry in the positive ion MRM mode. Good linearity was achieved over a wide range of 0.01–20 μg/mL. The intra- and inter-batch precisions (as RSD, %) were less than 7.1%. The average extraction recovery was 87.5%. The method described above has been used, for the first time, to reveal the pharmacokinetics of mildronate injection in healthy subjects. After single intravenously administration of 250, 500 and 1000 mg mildronate, the elimination half-life (t_1/2) were (5.56 ± 1.55), (6.46 ± 1.07) and (6.55 ± 1.17) h, respectively. The Student–Newman–Keuls test results showed that peak plasma concentration (C_max) and the area under the plasma concentration versus time curve from time 0 to 24 h (AUC_0–24) were both linearly related to dose. The pharmacokinetics of mildronate fitted the linear dynamic feature over the dose range studied. The essential pharmacokinetic parameters of multidoses administration intravenously (500 mg, b.i.d) were as follows: t_1/2 was (15.34 ± 3.14) h; C_max was (25.50 ± 3.63) μg/mL; AUC_0–24 was (58.56 ± 5.57) mg h/L. The t_1/2 and AUC of multidoses administration intravenously were different from those of single-dose administration significantly. These findings suggested that accumulation of mildronate in plasma occurred.     

The influence of starvation on fast-start performance of Spinibarbus sinensis

Juvenile Spinibarbus sinensis (n = 48, body length, 5.86 ± 0.10 cm, 25 °C) were fasted for 0, 0.5, 1, 2, 4 and 6 weeks. The fast-start performances of the experimental fish were assessed using high-speed video photography and the locomotive kinematics analysis. The morphological parameters including tail height (H₂), tail length (L₂), lateral body area (S₁), median fin area (S₂), dorsal cross section area (S₃) and tail cross section area (S₄) were also measured using TpsDig and the Photoshop. The results showed that 6 week starvation resulted in significant decreases in the escape distance (d), maximum linear velocity (V_max) and maximum linear acceleration (a_max) of center of mass in Stage 1 and Stage 2 of fast-start process (P < 0.05), however there were two relatively sTable phases in the V_max and d, during the week 1–2 (V_max = 0.67 ± 0.06 mm/ms; d = 8.86 ± 0.73 mm) and week 4–6 (V_max = 0.31 ± 0.04 mm/ms; d = 3.70 ± 0.56 mm). When compared with the control group (0 week starvation group), only the 6 week starvation group showed the significantly different response time (t) with average t = 9.20 ± 0.37 ms in week 1–4. There were no significant difference in mass center turning angles at first stage (T_a1) , second stage (T_a2) and the sum of two stages (T_a(1+2)) was also not different (P > 0.05). The fish did not show any directional preference for left or right during escape turning, and all of the related parameters also remained unchanged among treatment group (P > 0.05). The areas of dorsal body cross-section decreased more acutely (P < 0.05) than caudal body cross-section (45.4% vs 38.0%) during the entire starvation period while no significant differences were observed in both the tail height and tail length among all treatment groups (P > 0.05). The results indicated that fast-start performance of juvenile S. sinensis is affected by the starvation; metabolic energy related traits such as the maximum linear velocity and the maximum linear acceleration decreased significantly after starvation; whereas traits with no direct link to metabolic energy such as the response time and turning angle remained unchanged during starvation. The lack of starvation induced change in the maneuverability of the fish suggests that fast-start ability related to escape strategy is relatively well conservative in juvenile S. sinensis.     

Clinical Outcomes Using Long-Term Combination Therapy with Insulin Glargine and Exenatide in Patients with Type 2 Diabetes Mellitus

ObjectiveTo examine the long-term effects of combination insulin glargine/exenatide treatment on glycemic control.MethodsWe conducted a 24-month retrospective US chart review of patients with inadequately controlled type 2 diabetes (T2DM) and hemoglobin A_1c (A1C) levels > 7.0% for whom glargine and exenatide were coprescribed in differing order (glargine added after exenatide [exenatide/glargine]; exenatide added after glargine [glargine/exenatide]). Treatment order groups were combined to form a pooled treatment group. Changes from baseline in A1C, patients with A1C ≤ 7.0%, body weight, glargine/exenatide daily dose, oral antidiabetic drug (OAD) use, and hypoglycemia were evaluated.ResultsTreatment groups were similar at baseline; however, patients in the glargine/exenatide group (n = 121) (vs exenatide/glargine group [n = 44]) had longer disease duration (11.8 vs 8.0 years) and took fewer OADs (1.7 vs 2.3). Overall, baseline A1C was 8.8 ± 1.3% and weight was 109.5 ± 25.3 kg. Significant A1C reductions emerged at month 6 and persisted throughout 24 months (vs baseline) in both treatment groups (pooled: –0.7 ± 1.6; P < .001), and 33.0% of patients achieved an A1C level ≤ 7.0%. After 24 months of exenatide/glargine, body weight remained unchanged (0.7 ± 8.3 kg; P = .640). With glargine/exenatide, body weight decreased (–2.5 ± 6.7 kg; P = .001). At month 24, daily glargine dose was 0.40 ± 0.23 units/kg for the exenatide/glargine group and 0.47 ± 0.30 units/kg for the glargine/exenatide group. Hypoglycemia frequency was similar in both treatment groups.ConclusionsRegardless of treatment order, long-term combined therapy with glargine and exenatide for up to 24 months in patients with inadequately controlled T2DM suggests reduction of A1C without significant weight gain or increased hypoglycemia risk. (Endocr Pract. 2012;18:17-25)     

Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise

The anion nitrate—abundant in our diet—has recently emerged as a major pool of nitric oxide (NO) synthase-independent NO production. Nitrate is reduced stepwise in vivo to nitrite and then NO and possibly other bioactive nitrogen oxides. This reductive pathway is enhanced during low oxygen tension and acidosis. A recent study shows a reduction in oxygen consumption during submaximal exercise attributable to dietary nitrate. We went on to study the effects of dietary nitrate on various physiological and biochemical parameters during maximal exercise. Nine healthy, nonsmoking volunteers (age 30 ± 2.3 years, VO_2max 3.72 ± 0.33 L/min) participated in this study, which had a randomized, double-blind crossover design. Subjects received dietary supplementation with sodium nitrate (0.1 mmol/kg/day) or placebo (NaCl) for 2 days before the test. This dose corresponds to the amount found in 100–300 g of a nitrate-rich vegetable such as spinach or beetroot. The maximal exercise tests consisted of an incremental exercise to exhaustion with combined arm and leg cranking on two separate ergometers. Dietary nitrate reduced VO_2max from 3.72 ± 0.33 to 3.62 ± 0.31 L/min, P < 0.05. Despite the reduction in VO_2max the time to exhaustion trended to an increase after nitrate supplementation (524 ± 31 vs 563 ± 30 s, P = 0.13). There was a correlation between the change in time to exhaustion and the change in VO_2max (R² = 0.47, P = 0.04). A moderate dietary dose of nitrate significantly reduces VO_2max during maximal exercise using a large active muscle mass. This reduction occurred with a trend toward increased time to exhaustion implying that two separate mechanisms are involved: one that reduces VO_2max and another that improves the energetic function of the working muscles.     

Exenatide Use in the Management of Metabolic Syndrome: A Retrospective Database Study

ObjectiveTo evaluate the effect of exenatide therapy on cardiometabolic risk factors and anthropometric parameters in patients with metabolic syndrome.MethodsFrom June 2005 to June 2007, we performed a retrospective analysis of data extracted from the records of adult patients with metabolic syndrome being treated with exenatide. Diagnosis of any type of diabetes mellitus was exclusionary. Patients were initiated on exenatide therapy, 5 mcg, 1 hour before their morning and evening meals for the first month and were instructed to titrate up to 10 mcg. Cardiometabolic risk factors (total cholesterol, high-denssity lipoprotein cholesterol, triglycerides, calculated low- density lipoprotein cholesterol, and blood pressure) and anthropometric parameters (absolute body weight, body mass index, and abdominal girth) were measured at baseline and at 16 ± 4 weeks after initiating exenatide therapy. Data collected also included age, sex, metabolic syndrome diagnosis, and other concomitant medication used in the management of endocrine disorders.ResultsThe study population consisted of 299 patients (259 women, 40 men) with an age range of 18 to 74 years. Exenatide treatment was associated with significant reductions in mean body weight (P < .001) and body mass index (P < .001). Weight loss in 76.6% of patients was concomitant with a significant reduction in mean abdominal girth (P < .001). Further analysis revealed significant decreases in mean triglycerides (P < .001), total cholesterol (P < .01), and both systolic (P < .01) and diastolic blood pressure (P < .03). Approximately 60.2% of patients used metformin concomitantly, and half either decreased or discontinued metformin therapy.ConclusionsThis is the first report examining the effect of exenatide on patients with metabolic syndrome. We observed a significant improvement in cardiometabolic risk factors and anthropometric parameters as a result of exenatide over the treatment interval. (Endocr Pract. 2008;14:993-999)     

Copper,zinc superoxide dismutase of Curcuma aromatica is a kinetically stable protein

This study details on cloning and characterization of Cu,Zn superoxide dismutase (Ca–Cu,Zn SOD) from a medicinally important plant species Curcuma aromatica. Ca–Cu,Zn SOD was 692 bp with an open reading frame of 459 bp. Expression of the gene in Escherichia coli cells followed by purification yielded the enzyme with K_m of 0.047 ± 0.008 μM and V_max of 1250 ± 24 units/mg of protein. The enzyme functioned (i) across a temperature range of −10 to +80 °C with temperature optima at 20 °C; and (ii) at pH range of 6–9 with optimum activity at pH 7.8. Ca–Cu,Zn SOD retained 50% of the maximum activity after autoclaving, and was stable at a wide storage pH ranging from 3 to 10. The enzyme tolerated varying concentrations of denaturating agent, reductants, inhibitors, trypsin, was fairly resistant to inactivation at 80 °C for 180 min (k_d, 6.54 ± 0.17 × 10⁻³ min⁻¹; t_1/2, 106.07 ± 2.68 min), and had midpoint of thermal transition (T_m) of 70.45 °C. The results suggested Ca–Cu,Zn SOD to be a kinetically stable protein that could be used for various industrial applications.     

The role of nest surface temperatures and the brain in influencing ant metabolic rates

Thermal limits of insects can be influenced by recent thermal history: here we used thermolimit respirometry to determine metabolic rate responses and thermal limits of the dominant meat ant, Iridomyrmex purpureus. Firstly, we tested the hypothesis that nest surface temperatures have a pervasive influence on thermal limits. Metabolic rates and activity of freshly field collected individuals were measured continuously while ramping temperatures from 44 °C to 62 °C at 0.25 °C/minute. At all the stages of thermolimit respirometry, metabolic rates were independent of nest surface temperatures, and CT_max did not differ between ants collected from nest with different surface temperatures. Secondly, we tested the effect of brain control on upper thermal limits of meat ants via ant decapitation experiments (‘headedness’). Decapitated ants exhibited similar upper critical temperature (CT_max) results to living ants (Decapitated 50.3±1.2 °C: Living 50.1±1.8 °C). Throughout the temperature ramping process, ‘headedness’ had a significant effect on metabolic rate in total (Decapitated V̇CO₂ 140±30 µl CO₂ mg⁻¹ min⁻¹: Living V̇CO₂ 250±50 CO₂ mg⁻¹ min⁻¹), as well as at temperatures below and above CT_max. At high temperatures (>44 °C) pre- CT_max the relationships between I. purpureus CT_max values and mass specific metabolic rates for living ants exhibited a negative slope whilst decapitated ants exhibited a positive slope. The decapitated ants also had a significantly higher Q₁₀:25–35 °C when compared to living ants (1.91±0.43 vs. 1.29±0.35). Our findings suggest that physiological responses of ants may be able to cope with increasing surface temperatures, as shown by metabolic rates across the thermolimit continuum, making them physiologically resilient to a rapidly changing climate. We also demonstrate that the brain plays a role in respiration, but critical thermal limits are independent of respiration levels.     

Nonobese Young Females with Polycystic Ovary Syndrome Have Nutritive Microvascular Dysfunction: A Pilot Study

ObjectiveTo investigate nutritive microvascular function in young nonobese females with polycystic ovary syndrome (PCOS) and to correlate microvascular reactivity with sex steroids, inflammatory markers, and metabolic variables.MethodsFourteen nonobese females with PCOS (24.6 ± 2.7 years, body mass index [BMI] 23.7 ± 3.1 kg/ m²) and 13 age- and BMI-matched controls (22.8 ± 2.3 years, 22.5 ± 3.4kg/m2) underwent anthropometric, hormonal, and microvascular evaluations. The main outcome measures were capillary density, red blood cell velocity (RBCV) at resting and peak during postocclusive reactive hyperemia (RBCV_max), and time taken to reach RBCV_max (TRBCV_max).ResultsSubjects with PCOS had lower RBCV and higher TRBCV_max compared to controls, respectively (0.237 [0.220-0.324] vs. 0.362 [0.297-0.382] mm/s, F < .01) and (5 [5-6] vs. 4 [3-5] s, P < .05]. The free androgen index (FAI) and sex hormone-binding globulin (SHBG) level were different between groups. FAI correlated to RBCV_max (ρ = -0.49, P < .05) and to TRBCV_max (ρ = 0.41, P < .05). SHBG correlated with RBCV_max (ρ = 0.52, P < .01) while estradiol (E₂) levels correlated with RBCV (ρ = 0.80, P < .001) and RBCV_max (ρ = 0.46, P < .05).ConclusionMicrovascular dysfunction characterized by reduced RBCV_maxand prolonged TRBCV_maxwas present in young, nonobese PCOS subjects. FAI was associated with observed impairments, suggesting a possible common mechanism linking sex hormones and microvascular dysfunction. (Endocr Pract. 2014;20:1281-1289)     

The effectiveness of stretch–shortening cycling in upper-limb extensor muscles during elite cross-country skiing with the double-poling technique

This investigation was designed to evaluate the effectiveness of stretch–shortening cycling (SSC_EFF) in upper-limb extensor muscles while cross-country skiing using the double-poling technique (DP). To this end, SSC_EFF was analyzed in relation to DP velocity and performance. Eleven elite cross-country skiers performed an incremental test to determine maximal DP velocity (V_max). Thereafter, cycle characteristics, elbow joint kinematics and poling forces were monitored on a treadmill while skiing at two sub-maximal and racing velocity (85% of V_max). The average EMG activities of the triceps brachii and latissimus dorsi muscles were determined during the flexion and extension sub-phases of the poling cycle (EMG_FLEX, EMG_EXT), as well as prior to pole plant (EMG_PRE). SSC_EFF was defined as the ratio of aEMG_FLEX to aEMG_EXT. EMG_PRE and EMG_FLEX increased with velocity for both muscles (P < 0.01), as did SSC_EFF (from 0.9 ± 0.3 to 1.3 ± 0.5 for the triceps brachii and from 0.9 ± 0.4 to 1.5 ± 0.5 for the latissimus dorsi) and poling force (from 253 ± 33 to 290 ± 36 N; P < 0.05). Furthermore, SSC_EFF was positively correlated to V_max, to EMG_PRE and EMG_FLEX (P < 0.05). The neuromuscular adaptations made at higher velocities, when more poling force must be applied to the ground, exert a major influence on the DP performance of elite cross-country skiers.     

Durability of Effects of Exenatide Treatment on Glycemic Control,Body Weight,Systolic Blood Pressure,C-Reactive Protein,and Triglyceride Concentrations

ObjectiveTo determine (1) whether long-term treatment with exenatide is associated with reductions in C-reactive protein (CRP), systolic blood pressure (BP), and triglyceride concentrations in addition to reductions in body weight and hemoglobin A1c (A1C) levels and (2) whether these beneficial results persist without any loss of effect while exenatide is being used, and whether they reverse after its cessation.MethodsWe conducted a retrospective review of 141 patients with type 2 diabetes mellitus treated with exenatide at a tertiary clinic.ResultsExenatide (mean duration of treatment, 1.4 years) decreased A1C (0.7%), weight (5 kg), systolic BP (8 mm Hg), and triglyceride concentrations (46 mg/dL) (P < .05 for all). Sixty-one patients continued exenatide therapy throughout the study (mean duration of use, 2.4 years). Exenatide treatment reduced their mean weight by 7 kg, systolic BP by 8 mm Hg, triglycerides by 52 mg/dL, A1C by 1.3%, and CRP by 2.4 mg/L (P < .05 for all). Reductions in systolic BP and CRP were not related to weight loss. The reduction in CRP concentration was significantly related to the baseline CRP concentration (r = 0.78; P < .001) and to change in A1C (r = 0.68; P = .02). Patients who stopped taking exenatide had a reversal of the benefits within 6 months after cessation of treatment.Conclusion:Exenatide treatment in patients with type 2 diabetes has durable and persistent beneficial effects on A1C, weight, CRP, systolic BP, and triglyceride concentrations. Cessation of treatment reverses all these beneficial effects within 6 months. There was no evidence of loss of its effects while exenatide treatment was continued. (Endocr Pract. 2011;17:192-200)     

Algorithmic detection of the beginning and end of bipolar electrograms: Implications for novel methods to assess local activation time during atrial tachycardia

Activation mapping is required to effectively ablate atrial tachycardia (AT). Conventional tools to assess local activation time (LAT) are based upon the peak of the bipolar electrogram (B-EGM, LAT_Peak) and the maximal negative slope of the unipolar electrogram (U-EGM, LAT_Slope). Bipolar electrograms are influenced by wavefront direction, bipole orientation, and inter-electrode spacing causing ambiguity in peak detection, whereas unipolar electrograms are disturbed by the presence of far-field signals. We developed a new algorithm to detect the beginning and end of bipolar electrograms (t_begin and t_end). Then, we introduced new LAT methods related to the onset of B-EGMs (LAT_Onset), the center of mass of B-EGMs (LAT_CoM), and the slope of U-EGMs within a pre-defined window (LAT_Slope-hybrid).In total 3752 recordings from 31 AT patients were retrospectively analyzed. The signal-to-noise ratio (SNR) for B-EGMs was calculated to differentiate algorithmically high from low quality electrograms (HQ and LQ). In a subset of 328 B-EGMs, five experts validated the t_begin as determined by the algorithm by visual rating. The newly developed LAT methods were compared to the conventional LAT methods and to one another (Bland–Altman plots) in both HQ (n = 3003) and LQ EGMs (n = 749).The t_begin algorithm was accurate (deviation < ±10 ms) in 96 ± 4% of HQ and 91 ± 8% of LQ B-EGMs. BA plots revealed the following difference (bias) and variation in HQ and LQ EGMs respectively: (1) LAT_Onset vs. LAT_Peak: 27 ± 30 ms and 24 ± 62 ms; (2) LAT_CoM vs. LAT_Peak: 0 ± 16 ms and 2 ± 38 ms; (3) LAT_Slope-hybrid vs. LAT_Slope: 1 ± 32 ms and 15 ± 110 ms; (4) LAT_Onset vs. LAT_CoM: 22 ± 24 ms and 18 ± 22 ms; (5) LAT_Onset vs. LAT_Slope-hybrid: 16 ± 18 ms and 13 ± 22 ms; and (6) LAT_CoM vs. LAT_Slope-hybrid: 5 ± 20 ms and 4 ± 18 ms.In the present study, we introduced three new methods to assess local activation time in AT, based upon an algorithm detecting accurately the beginning and end of the B-EGM complex. BA analysis of the new methods showed similar variation in high and low quality EGMs, suggesting that they introduce less ambiguity than the conventional peak method. LAT_Onset consistently yielded an earlier activation moment. LAT_Slope-hybrid – by blanking far-field potentials – seems to be the optimal method for detection of the maximal negative slope in U-EGMs. Interestingly, LAT_CoM in B-EGMs coincided with the maximal negative slope in U-EGMs, suggesting its physiological sense and future use. The new LAT methods can be implemented in real-time mapping applications.     

Découverte fortuite de fixations colorectales focales du FDG en TEP/TDM : corrélation aux données de la coloscopie

PurposeFDG-PET is an established tool for the diagnosis of recurrent or metastatic colorectal carcinoma. Several case series suggest that FDG-PET often detects incidental adenomatous polyps or colorectal adenocarcinomas. The aim of this study was to correlate unexpected colorectal foci of FDG uptake to pathology findings after systematic colonoscopy.Patients and methodsWe reviewed the records of 3541 patients who underwent FDG PET/CT in our institution over a 30-month period for the assessment of a known or suspected malignancy. In 85 of them, incidental, nodular shaped and well-circumscribed foci of abnormal uptake were identified in the area of the colon or rectum. Patients with segmental or diffuse abnormal colorectal uptake were excluded, as well as patients with known benign or malignant colorectal disease. Colonoscopy and complete pathology report was available in 29 patients. Maximal standardized uptake value (SUV_max) was measured in all lesions.ResultsUnexpected colorectal foci of FDG uptake were associated with colonoscopic abnormalities in 23 patients (true positive rate: 79 %). Adenocarcinomas were found in six patients (SUV_max = 7.3 ± 2.6), tubulous adenomas in four patients (SUV_max = 7.3 ± 4.9) and tubulovillous adenomas in 12 patients (SUV_max = 4.2 ± 1.1). Hyperplasic polyps with no sign of dysplasia were found in the last patient (SUV_max = 3.3). Concomitant CT abnormalities were found on PET/CT fusion in eight patients and consisted of wall thickening (n = 5) or nodular mass (n = 3). Conversely, PET was falsely positive in six patients (21 %), with no concomitant CT abnormalities and no abnormal findings at endoscopy (SUV_max = 6.2 ± 2.8, no significant difference with true positive lesions).ConclusionOur findings emphasize the need to perform a colonoscopy in front of incidental nodular colorectal foci of FDG uptake because malignant or pre-malignant neoplasms, which are not clinically apparent, are found in more than three-quarter of cases.     

Détermination par TEP-TDM au 18FDG du statut ganglionnaire dans les cancers du col utérin – intérêt de la mesure du SUV de la tumeur primitive

Purpose. – To evaluate the value of ¹⁸F-fluoro-2-désoxyglucose (FDG) PET-CT and maximal standardized uptake value (SUV_max) of the primary tumor for lymph node staging in cervical cancer.Materials and methods. – This retrospective study involved a series of 18 consecutive patients who had benefited from PET-CT and MRI at initial staging for a stage IB or higher cervical carcinoma. The SUV_max of each primary tumor was measured retrospectively. All patients had been previously treated by radiochemotherapy. Lymph node status was obtained in 12 of 18 cases.Results. – The sensitivity and specificity for determining lymph node status was 80 and 86%, respectively, for PET-CT, and 80 and 71% for MRI. In 16.6% of cases, PET-CT revealed unknown sus-diaphragmatic lesions. SUV_max of the primary tumor was significantly higher in the N+ than in the N− group (15.6 ± 1.6 vs 8.5 ± 3.9, p < 0.01). The optimal threshold was determined to be 10.8 from ROC analysis.Conclusion. – When staging with FDG PET-CT, SUV_max of a primary cervical cancer seems to be a good predictor of lymph node status. This could lead to an intensification of treatment for patients whose SUV_max is higher than 10.8. A prospective study would allow to assess a potential benefit of treatment intensification for patients with SUV_max higher than 10.8.     

Characterization and localization of the endothelin receptors in human end-stage heart failure: ETA/ETB receptor system—Role in the failing human heart

Endothelin (ET) is a potent vasoconstrictor peptide implicated in numerous human diseases, including ischemic cardiomyopathy (ICM). ET binds to receptors ET_A and ET_B. Specific ET receptors were characterized in left atria of patients with end-stage heart failure due to ischemic cardiomyopathy (ICM) (n = 9) and healthy controls (n = 9). Saturation assays revealed a K_d and B_max of 28 ± 8 pM and 87 ± 22 fmol mg^?1 of protein, respectively, from healthy atria and 50 ± 9 pM and 162 ± 19 fmol mg^?1 of protein, respectively, from diseased atria (p < 0.05). For competition studies, we obtained a percentage of ET_A receptors using BQ123, 55% ± 5 and 66% ± 4 in healthy and diseased atria, respectively (p < 0.05). The percentage of ET_B using BQ3020 was 55% ± 14 in healthy and 59% ± 10 in diseased atria. Microautoradiography studies showed a greater number of ET receptors, predominately ET_A, existed in the myocardial layer of diseased atria compared with healthy atria. The percentage of occupied area was greater in the endocardium than the epicardium in diseased atria. These results showed an increase in the ET_A/ET_B receptor system in the failing human heart compared with the non-failing human heart.     

Microspheres of chitosan/carboxymethyl cashew gum (CH/CMCG): Effect of chitosan molar mass and CMCG degree of substitution on the swelling and BSA release

Chitosan/carboxymethyl cashew gum microspheres (CH/CMCG) were prepared with carboxymethyl cashew gum with two different degrees of substitution (DS) and loaded with bovine serum albumin (BSA). In water, for microspheres formed using low molar mass chitosan (LCH) sample swelling was observed for both CMCG samples and CMCG sample with higher DS showed greater swelling. Using high molar mass chitosan (HCH) sample swelling was observed only for microsphere with high DS of CMCG (DS = 0.44). At pH 7.4, the HCH sample led to a lower degree of swelling. The diffusion coefficients D_v were higher for the higher DS of CMCG in both media and the HCH sample had a lower D_v than LCH one. Faster BSA release rates were observed for beads prepared with the higher DS, whereas those prepared with DS = 0.16 took twice the time to reach similar release profiles. All microsphere systems investigated had a non-Fickian BSA release mechanism.     

Association of urinary 15-F2t-isoprostane level with oxygen desaturation and carotid intima–media thickness in nonobese sleep apnea patients

Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may unbalance oxidative stress, increasing atherosclerosis. Among oxidative stress markers, 15-F_2t-isoprostane is considered one of the most sensitive and specific metabolites of lipid peroxidation. To explore the relationship between urinary 15-F_2t-isoprostane with sleep apnea severity and carotid modifications in nonobese OSA patients, 31 nonobese sleep apnea patients were studied, along with 10 lean subjects without OSA. Patients were assessed by polysomnography, blood pressure measurement, and ultrasonography to determine the carotid intima–media thickness (IMT). Urinary 15-F_2t-isoprostanes were measured by liquid chromatography–tandem mass spectrometry. Urinary 15-F_2t-isoprostane concentrations were increased in severe OSA patients compared to control subjects (20.2 ± 7.3 vs 12.3 ± 2.8 ng/mmol creatinine; P = 0.020). Mean carotid IMT was correlated with 15-F_2t-isoprostane (r = 0.532; P < 0.001) and with the apnea–hypopnea index (r = 0.345; P = 0.029). 15-F_2t-Isoprostane level was related to the night time spent at SaO₂ < 90% (r = 0.478; P = 0.002), the apnea–hypopnea index (r = 0.465; P = 0.003), and the mean nocturnal SaO₂ (r = ? 0.424; P = 0.007). These results showed a relationship between lipid peroxidation, carotid intima–media thickness, and intermittent hypoxia in nonobese OSA patients, thus reinforcing the hypothesis that oxidative stress could be involved in the early atherosclerotic process.