Risperidone and liver function tests in children and adolescents: a short-term prospective study

OBJECTIVE: Revealing of unknown adverse effects of atypical antipsychotics on pediatric population may take a long period of time. The purpose of this prospective study is to document changes in the liver function tests (LFTs) associated with risperidone usage in a group of children and adolescents. METHOD: Study subjects consist of 120 youths with ages ranging from 3-17 years. For this study, patients' baseline and follow-up weight and hepatobiliary function tests including alanine aminotransferases(ALT) and aspartat aminotransferases (AST), gamma gluatamyl transerase (GGT), alkaline phosphatase (ALP) and serum bilirubin levels were measured before and after the treatment period of one month. RESULTS: Only one male patient's ALT levels increased up to three-fold and AST levels increased up to two-fold of the basal levels. First month mean levels of liver enzymes and billuribin of the patients were significantly higher than the baseline. Sixty-three patients (52.5%) showed an asymptomatic increase in the liver enzymes and/or billuribin levels of the first month of this study. Weight gain was observed in 58 patients (57.4%). There was no significant association between changes in weight and liver enzymes and billuribin levels. CONCLUSION: We found clinically non significant liver function test abnormalities mostly in the form of ALP elevation in 52.5% and marked liver enzymes elevation in 0.8% of risperidone-treated subjects. However use of concomitant medications and variations in age are the limitations of this study. These findings suggest that risperidone treatment in the short term may lead to liver function changes in children and adolescents.     

Impact of beta-blockers on sleep in patients with mild hypertension: a randomized trial between nebivolol and metoprolol

Introduction  Sleep is an innate and essential part of human life. Various aspects of sleep are negatively affected by beta-blockers. We compared the impact of two beta-blockers, metoprolol succinate (extended release) and nebivolol, on sleep quality in patients with stage 1 hypertension. Methods  This was a prospective, randomized, open-label, parallel-group study. Eligible patients were administered the Pittsburgh Sleep Quality Index (PSQI) questionnaire by a blinded interviewer and were randomized to receive metoprolol (starting dose 25 mg) or nebivolol (starting dose 2.5 mg) once daily for 6 weeks. The first dose was administered before patients left the clinic. Visits were scheduled for 1, 2, 4, and 6 weeks after the initiation of therapy. At the end of the study, patients were readministered the PSQI questionnaire by the same interviewer, as before blinded to treatment allocation. Results  A total of 22 patients in the nebivolol group and 17 patients in the metoprolol group completed the study and were included in the data analysis (mean age of patients, 40.7 years). At study entry, systolic blood pressure (BP), diastolic BP, and PSQI scores were similar in the two groups. Over 6 weeks of treatment, systolic and diastolic BP normalized in both groups. Global PSQI score improved significantly in patients in the nebivolol group, whereas it worsened in the metoprolol group. The difference in effect of two beta-blockers was statistically significant (P<0.001). Conclusion  Nebivolol was associated with improved sleep (as assessed by the PSQI), whereas metoprolol was associated with a worsening of sleep characteristics.     

Ultrastructural damage in lung tissues in rats treated with doxorubicin and paclitaxel

Introduction

The aim of this study was to determine the ultrastructural effects of doxorubicin (Adriblastina®; Pharmacia and Upjohn, Milan, Italy), paclitaxel (Taxol®; BMS, Princeton, NJ), Cremophor® EL (a diluent of paclitaxel) and doxorubicin/paclitaxel combinations on normal lung tissues.

Methods

In the experimental protocol, 50 Wistar albino rats were used, divided into five different groups: the control group (n=10), the doxorubicin group (1 mg/kg) (n=10), the paclitaxel group (2 mg/kg) (n=10), the Cremophor EL group (150 mg/kg) (n=10) and the paclitaxel/doxorubicin group (2 mg/kg+ 1 mg/kg) (n=10). The drugs were administered weekly to rats via intraperitoneal injections for 14 weeks. After 3 weeks of observation, the rats were killed with thiopental sodium (30 mg/kg) and their left median lung tissues were removed and examined with a Carl Zeiss EM 900 transmission electron microscope.

Results

Our experiments showed doxorubicin to cause an increase in collagen fibre content of the alveolar wall, and paclitaxel to cause degenerations in cellular organelles. In the group in which the two agents were administered together, both effects were observed, although the effects of paclitaxel were seen to be dominant. Ultrastructural appearance was similar in the Cremophor EL group compared to the control group.

Conclusion

It was detected that doxorubicin and paclitaxel caused ultrastructural degenerations in normal lung tissues and Cremophor EL seemed to be unaccountable for these degenerations.

     

Soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) is decreased in lung cancer patients showing progression: a pilot study

Tumor growth and metastasis depend on angiogenesis, and the vascular endothelial growth factor (VEGF) is known to be one of the most important angiogenic factors although the knowledge about its receptors is limited. We, therefore, investigated the treatment-related changes both in the level of the soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) in the serum by ELISA and the expression of VEGFR-1 in cancer tissues by immunohistochemistry. The serum levels were studied in 38 lung cancer patients, and 55 control subjects (21 benign disease and 34 healthy subjects) before the chemotherapy. The treatment-related changes in serum sVEGFR-1 were evaluated in 15 patients 24 and 48 hours after treatment. In addition to serum analysis, the tissue expressions were evaluated in 32 patients before treatment. The treatment-related changes in tissue VEGFR-1 expressions were evaluated in only 12 patients 24 hours after treatment. We observed no significant difference in terms of serum sVEGFR-1 levels between malignant and nonmalignant groups (p > 0.05). There were no significant differences in the levels of sVEGFR-1 before and after treatment (p > 0.05). However, there was a significant difference between sVEGFR-1 levels in the groups (regressive, stable, progressive) classified according to the response to therapy (p = 0.043). A significant difference also was present between the expression levels of tissue VEGFR-1 in the same groups (p = 0.037). As a conclusion, we suggest that prechemotherapy sVEGFR-1 can be helpful for prediction of long-term response to therapy, but it should be studied in larger groups to elucidate its benefit in clinics.     

Protective effects of caffeic acid phenethyl ester, vitamin C, vitamin E and N-acetylcysteine on vancomycin-induced nephrotoxicity in rats

The objective of this study was to compare the beneficial effects of caffeic acid phenethyl ester (CAPE), vitamin C, vitamin E and N-acetylcysteine on vancomycin-induced nephrotoxicity. Thirty rats were randomly devided into six groups: (i) control; (ii) vancomycin, 200 mg/kg administrated via intraperitoneal route; (iii) vancomycin plus CAPE-vancomycin with 10 micromol/kg CAPE; (iv) vancomycin plus vitamin C-vancomycin (intraperitoneally) with 200 mg/dl vitamin C in drinking water; (v) vancomycin plus vitamin E-vancomycin with 1000 mg/kg body weight vitamin E (intramuscularly); and (vi) vancomycin plus N-acetylcysteine-vancomycin with 10 mg/kg body weight (intraperitoneally) of N-acetylcysteine. Vancomycin treatments were started 1 day after the first administrations of these agents and continued for 7 days. At the end of the experiments, catalase activity was significantly decreased by vancomycin in kidney homogenates (P < 0.05). Vitamin E, vitamin C, N-acetylcysteine and CAPE administrations decreased the blood urea nitrogen levels increased by vancomycin, although significant differences were detected only in the vitamins E and C groups (P < 0.05). Increased renal malondialdehyde and nitric oxide levels by vancomycin were significantly suppressed by agents used in the study (P < 0.05). Histopathological examination demonstrated prominent damages in the vancomycin-treated group. Vitamin E was the most beneficial agent on vancomycin-induced tubular damage, followed by vitamin C, N-acetylcysteine and CAPE treatments, respectively. The data suggest that vitamin E, as well as vitamin C, N-acetylcysteine and CAPE, could be useful for reducing the detrimental effects on vancomycin-induced toxicity in kidneys.     

Nanoparticles featuring amino acid-functionalized side chains as DNA receptors

A family of nanoparticles has been fabricated featuring cationic amino acid-based side chains. This controlled surface modification provides a tool to investigate the effect of various non-covalent interactions at the nanoparticle-DNA interface. The binding affinities of these nanoparticles towards DNA were determined using fluorescence, exhibiting more than threefold modulation in binding a 37-mer DNA strand. The secondary structure of the DNA strand was distorted upon nanoparticle binding, with the extent of distortion dependent on the structure of amino acid side chain.     

Survival benefit with GM-CSF use after high-dose chemotherapy in high-risk breast cancer

AIMS AND BACKGROUND: The role of high-dose chemotherapy in breast cancer has not been fully defined. It has been concluded that new trials should focus on defining potential subgroups that are more likely to benefit from high-dose chemotherapy. We compared survival differences in patients receiving human granulocyte-colony stimulating factor (G-CSF) or granulocyte-monocyte colony stimulating factor (GM-CSF) after high-dose chemotherapy with stem cell support. METHODS: High-risk non-metastatic breast cancer patients (axillary lymph node involvement more than 8) aged 16 to 65 years and with a performance status < or = 1 underwent high-dose chemotherapy with autograft. Written informed consent was obtained from every patient, and the study was approved by the local ethics committee. RESULTS: For 54 eligible women, the median follow-up was 41.4 months. The five-year disease-free survival was 45.7%. The five-year projected overall survival rate was 53.9%. Among them, patients who received GM-CSF (n = 12) posttransplant lived longer than the patients who received G-CSF (n = 15) (five year survival rates, 46.6% vs 75%, P < 0.050). The patients who received GM-CSF posttransplant had fewer relapses (5 vs 9). However, between the two groups there was no statistically significant difference regarding disease-free survival rates calculated with the Kaplan-Meier method (58.8% vs 40%; P = 0.121). CONCLUSIONS: Patients receiving GM-CSF posttransplant lived longer and they had fewer relapses than those who received G-CSF. This result merits consideration. The antitumor activity of GM-CSF should be investigated further in prospective randomized trials.