Effects of exenatide twice daily versus sitagliptin on 24-h glucose, glucoregulatory and hormonal measures: a randomized, double-blind, crossover study.

AIM: To compare exenatide and sitagliptin glucose and glucoregulatory measures in subjects with type 2 diabetes. METHODS: An 8-week, double-blind, randomized, crossover, single-centre study. Eighty-six subjects (58% female, body mass index 35 ± 5 kg/m², haemoglobin A1c 8.3 ± 1.0%) received either exenatide 10 µg (subcutaneous) twice daily or sitagliptin 100 mg (oral) daily for 4 weeks and crossed to the other therapy for an additional 4 weeks. Main outcome was time-averaged glucose during the 24-h inpatient visits. RESULTS: Both treatments decreased average 24-h glucose, but exenatide had a greater effect [between-group difference: -0.67 mmol/l, 95% confidence interval (CI): -0.9 to -0.4 mmol/l]. Both treatments decreased 2-h postprandial glucose (PPG), area under the curve of glucose above 7.8 mmol/l (140 mg/dl) and 11 mmol/l (200 mg/dl) and increased the time spent with glucose between 3.9 and 7.8 mmol/l (70 and 140 mg/dl) during 24 h, but exenatide had a significantly greater effect (p < 0.05). Both treatments decreased postprandial serum glucagon, with exenatide having a greater effect (p < 0.005). Both treatments decreased fasting blood glucose to a similar degree (p = 0.766). Sitagliptin increased, while exenatide decreased, postprandial intact glucagon-like peptide-1. Both drugs improved homeostasis model assessment of ß-cell function (HOMA-B), with exenatide having a significantly greater effect (p = 0.005). Both exenatide and sitagliptin decreased 24-h caloric intake, with exenatide having a greater effect (p < 0.001). There was no episode of major hypoglycaemia. Adverse events were mild to moderate and mostly gastrointestinal in nature with exenatide. No study withdrawals were due to an adverse event. CONCLUSION: Compared to sitagliptin, exenatide showed significantly lower average 24-h glucose, 2-h PPG, glucagon, caloric intake and improved HOMA-B.

The cardiovascular and cardiac actions of ecstasy and its metabolites.

The recreational use of 3, 4 methylenedioxymethamphetamine (ecstasy or MDMA) has increased dramatically over the past thirty years due to its ability to increase stamina and produce feelings of emotional closeness and wellbeing. In spite of the popular perception that MDMA is a safe drug, there is a large literature documenting that the drug can produce significant neurotoxicity, especially in serotonergic and catecholaminergic systems. There are also experimental and clinical data which document that MDMA can alter cardiovascular function and produce cardiac toxicity, including rhythm disturbances, infarction and sudden death. This manuscript will review the literature documenting the cardiovascular responses elicited by MDMA in humans and experimental animals and will examine the underlying mechanisms mediating these responses. We will also review the available clinical, autopsy and experimental data linking MDMA with cardiac toxicity. Most available data indicate that oxidative stress plays an important role in the cardiotoxic actions of MDMA. Moreover, new data indicates that redox active metabolites of MDMA may play especially important roles in MDMA induced toxicity.

Quantitation of human heme oxygenase (HO-1) copies by competitive RT-PCR.

The authors have developed a system for quantifying human HO-1 mRNA in samples limited in cell number and/or mRNA copies. Total RNA from human liver was used to develop the system. The RNA is reverse transcribed and amplified by PCR in a tube also containing an internal standard obtained by deleting 50 base pairs from the original human gene. After amplification the two templates are resolved and quantified. When the internal standard is present in the reaction mixture, the ratio of amplified sample to internal standard is proportional to the amount of sample RNA making it possible to calculate the number of specific mRNA molecules.