Thyroid dysfunction associated with increased low-density lipoprotein cholesterol in epileptic children treated with carbamazepine monotherapy: a causal relationship?

OBJECTIVE: Lipid abnormalities and thyroid dysfunction have been reported in patients treated with antiepileptic drugs. The aim of this study was to evaluate prospectively the association between thyroid and lipid profile in children treated with carbamazepine (CBZ) monotherapy. MATERIALS AND METHODS: Thyroid function was evaluated in 18 epileptic children, previously reported with CBZ-induced changes in serum lipid profile, before and at 6, 12 and 24 months of CBZ monotherapy. RESULTS: All children had normal thyroid function before the initiation of CBZ treatment. During CBZ therapy thyroid dysfunction, with increased thyrotropin (TSH) and decreased thyroxine (T4), free thyroxine (FT4) and triiodothyronine (T3) was found, while, significant association was revealed between serum low-density lipoprotein cholesterol (LDL-C) and TSH levels at 6 (r=0.469; p=0.043) and 12 (r=0.730; p=0.001) months of treatment. CONCLUSION: Lipid abnormalities may be associated with thyroid hormone disturbance in children treated with CBZ monotherapy. Since thyroid dysfunction and hypercholesterolemia are both associated with a higher atherosclerotic risk special attention and further studies are needed in epileptic patients treated with CBZ monotherapy.

Effect of U-74389G (21-lazaroid) on intestinal recovery after acute mesenteric ischemia and reperfusion in rats.

Although it has been demonstrated that lazaroids can protect various organs from ischemia reperfusion injury, results obtained in the small intestine have been conflicting. On the other hand, it is not known whether inhibition of lipid peroxidation prevents intestinal ishemia-reperfusion injury. We investigated whether the administration of the aminolazaroid U-74389G had a beneficial effect on the repair process of the intestinal mucosa after transient mesenteric ischemia in a randomized-blind trial. Six groups of rats were subjected to a model of 60 min of intestinal ischemia that was produced by occluding the superior mesenteric artery. At the end of ischemia, U-74389G was administered intravenously and the clamp was removed to allow reperfusion. At 60 min after reperfusion animals were sacrificed and a 10-cm section of terminal ileum was resected. Its efficacy was evaluated by histopathological assessment, measurement of polymorphonuclear leukocytes and the extent of lipid peroxidation by measuring the small intestine tissue malondialdehyde. After 1 h of reperfusion, mucosal damage in both U-74389G-treated rats and control group rats was similar. However, the number of polymorphonuclear leukocytes in the intestinal mucosa was lower in the U-74389G group. Of particular interest was that U-74389G resulted in a statistically significant reduction in the concentration of small intestine tissue malondialdehyde, compared to the controls. When administered in an imitated clinical setting, U-74389G did not prevent intestinal ischemia reperfusion injury, however it protected the rat small intestine from oxidative damage by inhibiting lipid peroxidation.

Protective effect of a novel antioxidant non-steroidal anti-inflammatory agent (compound IA) on intestinal viability after acute mesenteric ischemia and reperfusion.

Reactive oxygen species play an important role in the basic pathophysiology of ischemia-reperfusion injury. We investigated whether the administration of a novel non-steroidal anti-inflammatory compound with antioxidant properties, the compound [5-(2-amino-ethylamino)-1-phenyl-2-pentanone] (compound IA), has a beneficial effect on the repair process of the intestinal mucosa after transient mesenteric ischemia in a randomized blind trial. Six groups of rats were subjected to a model of 60 min of intestinal ischemia that was produced by occluding the superior mesenteric artery. At the end of ischemia, compound IA was administered intravenously and the clamp was removed allowing reperfusion. At 60 min after reperfusion, animals were sacrificed and a 10 cm section of terminal ileum was resected. The outcome was evaluated by histopathologic assessment, measurement of polymorphonuclear leukocytes and the extent of lipid peroxidation measuring the small intestine tissue malondialdehyde. After 1 h of reperfusion, the mucosal damage was less in IA-treated rats compared with the control group. Moreover, the number of polymorphonuclear leukocytes in intestinal mucosa was significantly lower in IA group. Compound IA resulted in a statistically significant reduction of the concentration of small intestine tissue malondialdehyde, compared to those of controls. Administration of compound IA decreased the mucosal damage in rats that were subjected to 60 min of ischemia followed by 60 min of reperfusion. The mechanism of compound IA action is considered to be mediated via its potent antioxidant, free radical scavenging activities and inhibition of polymorphonuclear leukocytes infiltration.

Elevated intraesophageal pressure in patients with achalasia: a common and important manometric finding.

There is a subgroup of patients with achalasia in which manometry shows elevated intraesophageal pressure, expressed by elevation of esophageal baseline relative to gastric pressure. The aim of this study was to determine the prevalence of elevated intraesophageal pressure in patients with achalasia and its relationship to clinical, radiographic, endoscopic, and other manometric findings. Manometric studies of 62 patients with achalasia were analyzed and elevated intraesophageal pressure was considered any positive elevation of esophageal baseline relative to gastric pressure. Multiple regression analysis was used to determine independent risk factors associated with elevated intraesophageal pressure. Elevated intraesophageal pressure was found in 32 patients (51.6%). Lower esophageal sphincter pressure was the only independent variable associated with elevated intraesophageal pressure (P = 0.0167). Mean lower esophageal sphincter pressure was significantly higher in patients with elevated compared to those with normal intraesophageal pressure (34 +/- 1.96 vs 26.5 +/- 1.73 mm Hg; P = 0.006). In addition, lower esophageal sphincter pressure had a positive correlation with intraesophageal pressure (r = 0.49, P < 0.001). Conversely, no correlation was found between elevated intraesophageal pressure and various symptoms, disease duration, radiologic dilation, a finding of retained fluid during endoscopy, and esophageal length. We conclude that elevated intraesophageal pressure is a common manometric finding in patients with achalasia, with a prevalence of 51.6%, and is associated with significantly higher lower esophageal sphincter pressure.