The protective effect of amiodarone in lung tissue of cecal ligation and puncture-induced septic rats: a perspective from inflammatory cytokine release and oxidative stress

Sepsis is a serious medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. Amiodarone is a class III antiarrhythmic agent, a multichannel blocker (Ca++, Na+, and K+), and a noncompetitive α- and β-adrenergic blocker in cardiac cells. The present study aimed to determine whether amiodarone was protective against experimentally induced cecal ligation and puncture sepsis in rat lung tissue. The relationship between its probable protective effect and antioxidant/anticytokine action biochemically and histopathologically was also examined. Five groups of rats were used, each composed of 20 rats: (1) the sham-operated control group; (2) the CLP group; (3) the 25-mg/kg amiodarone-treated control healthy group; (4) the 50-mg/kg amiodarone-treated CLP group; and (5) the 50-mg/kg amiodarone-treated CLP group. A CLP polymicrobial sepsis model was applied to the rats. All groups were sacrificed 16 h later, and lung and blood samples were analyzed histopathologically and biochemically. Twenty-five and 50 mg/kg amiodarone decreased the level of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in serum and 8-iso-prostaglandin F2α level in lung tissue. They increased the activities of superoxide dismutase and levels of total glutathione in lung tissues of rats. Histopathological scores and examinations were in accordance with the biochemical results. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups. The CLP?+?amiodarone 50 mg/kg group had the lowest inflammation score among CLP groups. Our results indicate that administration of amiodarone prevented oxidative stress and cytokine action and protected lung tissue during sepsis cascade.     

The Prognosis and Survival of Childhood Acute Lymphoblastic Leukemia with Central Nervous System Relapse

Central nervous system (CNS) relapse in childhood acute lymphoblastic leukemia (ALL) has been overcome by sensitive therapatic approachs. This study was planned to present the development of CNS relapse and survival in newly diagnosed 190 ALL patients whose cases were followed in the authors' unit between March 1991 and May 2002. St. Jude Study XI protocol was given to the patients who applied between March 1991 and March 1997 (group A) (n = 122), and St. Jude Study XIII protocol was given to the patients who applied between March 1997 and May 2002 (group B) (n = 68). The patients having isolated CNS relapse in group A received craniospinal irradiation (CSI) median 3.5 months after CNS relapse (range 2–6 months), a short time after reinduction, and 2 cures of consolidation. In group B, patients having isolated CNS relapse received IT once a month and a high-dose methotrexate treatment once every 8 weeks and 3 or 4, cures later therapy CSI median 7 months after CNS relapse (range 6–8 months) was given. When the overall survival rates of the 2 groups are compared, a statistically significant higher survival rate at 5 years was determined in group B than in group A (respectively, 82.3%, 58.4%) (p < .05). When subgroups of the patients (that is, those with no relapse, isolated CNS or BM relapse, or CNS + BM relapse) were compared in both groups, it was found that survival was much higher for the ones with no relapse and with isolated CNS relapse (respectively, 87.9%, 72.7%) compared to isolated BM or CNS + BM relapse groups (respectively, 10%, 13.3%) (p < .05). In a conclusion, for children with acute lymphoblastic leukemia and an isolated CNS relapse, with delayed definitive craniospinal irradiation allowing more intensive systemic and intrathecal chemotherapy results in better overall survival than has been previously reported.     

Evaluation of the effect of tibolone and transdermal estradiol on triglyceride level in hypertriglyceridemic and normotriglyceridemic postmenopausal women

The objective of the present study was to quantify the magnitude of the association between the change in triglycerides and high-density lipoprotein (HDL) cholesterol levels with the use of tibolone and transdermal estrogen in postmenopausal women with hypertriglyceridemia and normotriglyceridemia. This prospective randomized study enrolled 140 postmenopausal women who had all been hysterectomized for almost a year or more. All subjects completed the 3-month follow-up. The 140 patients were divided into two groups: 70 were given transdermal 17β-estradiol 0.05 mg/day, and 70 were given tibolone 2.5 mg/day. We compared the effects of tibolone and transdermal 17β-estradiol on lipids and climacteric symptoms of the patients. To evaluate the effects of tibolone and transdermal estrogens on triglycerides and HDL cholesterol in postmenopausal women with normotriglyceridemia and hypertriglyceridemia, the women were assigned to five groups according to triglyceride levels (0-100, 101-200, 201-300, 301-400 and ? 401 mg/dl). We compared changes in the triglyceride and HDL cholesterol levels of each group after treatment. All 140 postmenopausal women completed the trial. No significant differences were found in baseline characteristics of the patients. The tibolone group showed a 22.6% decrease whereas the transdermal estrogen group had a 10.9% decrease in the mean triglyceride levels after 3 months of treatment. The mean decrease of triglyceride level with transdermal estradiol was approximately 11% in normotriglyceridemic and hypertriglyceridemic postmenopausal women. The mean decrease of triglyceride level was 17% in the normotriglyceridemic group and 22-30% in the hypertriglyceridemic groups with tibolone. While the mean HDL cholesterol level increased in the transdermal estrogen group (3.6%), it decreased in the tibolone group (9.3%). We found that tibolone decreased triglyceride levels much more than did transdermal estradiol. However, HDL cholesterol was decreased by tibolone and increased by transdermal estradiol. Tibolone had a more marked decreasing effect in postmenopausal women who had higher initial triglyceride levels. It is suggested that the beneficial effect of tibolone on the cardiovascular system might be greater in women with a high level of triglycerides.     

A rare metabolic complication of acute lymphoblastic leukemia in childhood: lactic acidosis

A 13-year-old boy presented with nausea, fatigue, weight loss, and bone pain for two months. Complete blood count and serum renal and liver function tests were all normal. Blood gas analysis revealed severe metabolic acidosis with high anion gap. Lactate level was 61.2 mmol/L. Abdominal ultrasonography yielded bilateral nephromegaly and hepatomegaly with increased echogenicity. Peripheral blood smear revealed 2% blasts. Bone marrow aspiration showed 'Common ALL Antigen'-negative acute lymphoblastic leukemia by flow cytometric analysis. Metabolic acidosis dissolved as soon as chemotherapy was begun. Lactic acidosis at the presentation of acute lymphoblastic leukemia--especially with low tumor burden--is a very rare and almost always fatal complication. Our patient is still alive and in remission, which is a point of interest in this child.     

Hashimoto thyroiditis associated with ataxia telangiectasia

Ataxia telangiectasia is a rare genetic disease characterized by neurological manifestations, infections, and cancers. In addition to these cardinal features, different autoimmune diseases can be seen in patients with ataxia telangiectasia. Although there were reports of positive autoimmune thyroid antibodies associated with ataxia telangiectasia, to our knowledge, we report the first cases of nodular Hashimoto thyroiditis in two patients with ataxia telangiectasia in the English medical literature. These cases illustrate that despite the rarity of nodular Hashimoto thyroiditis associated with ataxia telangiectasia, physicians should be aware of this possibility. Furthermore, thyroid examination of patient with ataxia telangiectasia is recommended for early diagnosis.     

Bilateral Ovariectomy in Young Rats: What Happens in Their Livers during Cecal Ligation and Puncture Induced Sepsis?

Study ObjectivePediatric ovarian masses comprise a heterogeneous group of benign and malignant lesions. Surgical methods consist of emergency or programmed surgery with tumoral resection and uni/bilateral oophorectomy or salpingo-oophorectomy. We examined whether bilateral ovariectomy (OVX) worsens liver injury during the onset of cecal ligation and puncture (CLP)-induced sepsis in rats.DesignThe rat groups were: sham, bilateral-OVX, sepsis, and OVX-sepsis.SettingsAfter OVX operation, rats were allowed to recover for 12 weeks. At the end of recovery, CLP was applied 16 hours after sepsis induction.Main OutcomeThere was a significant difference in the numerical density of hepatocytes only between the sepsis and the OVX-sepsis groups. Serum ALT and AST were increased significantly in the OVX-sepsis group. NF-κB activation after OVX increased after induction of sepsis. OVX-sepsis group showed marked thrombosis in portal vein branches and the central vein, degeneration in the bile ducts, and widespread ischemic areas in liver sections. Intra-inflammatory cell invasion was observed in both the portal and intrasinusoidal areas.DiscussionThis study indicates that increases in liver NF-κB activity in ovariectomized rats following CLP-induced sepsis correlates with elevated levels of serum ALT and AST and with histopathologic changes in rat liver. Bilateral OVX therefore appears to play a role in the activation of NF-κB or in production of cytokines in liver cells. Thus, we provided novel insight into the effects of OVX on liver injury following CLP-induced sepsis.