ABSTRACT
INTRODUCTION: Changes in hepatic clearance and CYP2D1 activity after combination therapy with insulin and metformin in type-1 diabetes and insulin administration in type-2 diabetes was assessed in an animal model. METHODS: Ten male Wistar rats were divided into two groups. Seven days after induction of diabetes, in treatment groups, type-1 diabetic rats received insulin plus metformin, and type-2 diabetic rats received insulin daily for 14 days. On day 21, rats were subjected to liver perfusion using Krebs-Henseleit buffer containing dextromethorphan as a CYP2D1 probe. Perfusate samples were analyzed by HPLC-FL. RESULTS: The average metabolic rate of dextromethorphan and hepatic clearance changed from 0.012 ± 0.004 and 6.3 ± 0.1 ml/min in the control group to 0.006 ± 0.001 and 5.2 ± 0.2 ml/min in the untreated type-1 diabetic group, and 0.008 ± 0.003 and 5 ± 0.6 ml/min in the untreated type-2 diabetic rats [1]. In the present study, metabolic rate and hepatic clearance changed to 0.0112 ± 0.0008 and 6.2 ± 0.1 ml/min in the type-1 diabetic group treated with insulin plus metformin, and 0.0149 ± 0.0012 and 6.03 ± 0.06 ml/min in the insulin-receiving type-2 diabetic rats. CONCLUSIONS: Administration of insulin plus metformin in type-1 diabetes could modulate the function of CYP2D1 to the observed levels in the control group and made it clearer to predict the fate of drugs that are metabolized by this enzyme. Moreover, good glycemic control with insulin administration has a significant effect on the balance between hepatic clearance and CYP2D1 activity in type-2 diabetes.
ABSTRACT
Fatigue is a common symptom in patients with Lyme disease. The purpose of this study was to characterize fatigue in untreated adult patients presenting with erythema migrans. Selected variables were assessed to determine if any correlated with the presence or severity of fatigue. Fatigue was assessed on the day of the evaluation by a Visual Analogue Scale (VAS), over the past 14days by the 11-item Fatigue Severity Scale (FSS-11) and over the past 28days based on a question from the 36-item Short Form General Health Survey version 2. Fifty-one patients with erythema migrans whose mean age was 49.8years, and 33 (64.7%) of whom were male, were evaluated in this study. The 3 measures of fatigue were positively correlated with one another (P≤0.01). Twenty-six (51%) had fatigue based on a VAS score above 0. Ten (19.6%) had severe fatigue based on an FSS-11 score of ≥4. The strongest correlate for higher fatigue scores was having a greater total number of symptoms. Based on the FSS-11 assessment tool, approximately 20% of early Lyme patients have severe fatigue. Having a high total number of symptoms was associated with both the presence and severity of fatigue. Because prior studies have demonstrated the presence of elevated levels of proinflammatory cytokines and other molecules in the serum of highly symptomatic patients with erythema migrans, the symptom of fatigue in early Lyme disease may be a component of what has been referred to as the acute sickness response.
