High dietary iron concentrations enhance the formation of cholesterol oxidation products in the liver of adult rats fed salmon oil with minimal effects on antioxidant status

The aim of this study was to investigate the effect of high dietary iron concentrations on the antioxidant status of rats fed two different types of fat. Four groups of male adult Sprague-Dawley rats were fed diets with adequate (50 mg iron supplemented per kg diet) or high (500 mg iron supplemented per kg diet) iron concentrations with either lard or salmon oil as dietary fat at 100 g/kg for 12 wk. The antioxidant status of the rats was profoundly influenced by the type of fat. Rats fed salmon oil diets had higher concentrations of thiobarbituric acid-reactive substances (TBARS) (P < 0.001), various cholesterol oxidation products (COP) (P < 0.001), total and oxidized glutathione (P < 0.05) and a lower concentration of alpha-tocopherol (P < 0.05) in liver and plasma than rats fed lard diets. The iron concentration of the diet did not influence the concentrations of TBARS, the activities of superoxide dismutase and glutathione peroxidase or the concentration of alpha-tocopherol in plasma or liver. The activity of catalase (P < 0.01) and the concentrations of total, oxidized and reduced glutathione (P < 0.05) in liver were slightly but significantly higher in rats fed high iron diets than in rats fed adequate iron diets, irrespective of the dietary fat. Rats fed the high iron diets with salmon oil, moreover, had higher concentrations of various COP in the liver (P < 0.001) than rats fed adequate iron diets with salmon oil. These results suggest that feeding a high iron diet does not generally affect the antioxidant status of rats but enhances the formation of COP, particularly if the diet is rich in polyunsaturated fatty acids.     

Carcinoma in situ in a lateral cervical cyst

BACKGROUND: The development of an invasive squamous cell carcinoma within a lateral cervical cyst as a result of malignant transformation of the epithelium is considered a rare circumstance. The existence of this entity is a source of controversy in light of the differential diagnosis, which includes a cervical metastasis from an unknown primary carcinoma (CUP-syndrome). Apart from site, histologic findings, and follow-up, the principal diagnostic criterion for lateral cervical cyst carcinoma is the histomorphologic demonstration of transition of the benign epithelium into invasive squamous cell carcinoma. Although numerous case reports of this entity exist, carcinoma in situ in a lateral cervical cyst has been reported in only five cases thus far. METHOD: In this context, we present the case of a 44-year-old patient with a 7-month history of cervical swelling. RESULTS: After diagnostic extirpation of the tumor, histologic findings were consistent with a lateral branchial cyst with high-grade dysplasia and carcinoma in situ of the squamous epithelial lining. CONCLUSION: This case of a premalignant lesion within a lateral branchial cyst (ie, carcinoma in situ) supplies the "missing link" and adds credibility to the concept of primary branchiogenic carcinoma.     

Determinants for receiving acupuncture for LBP and associated treatments: a prospective cohort study

Background  

Acupuncture is a frequently used but controversial adjunct to the treatment of chronic low back pain (LBP). Acupuncture is now considered to be effective for chronic LBP and health care systems are pressured to make a decision whether or not acupuncture should be covered. It has been suggested that providing such services might reduce the use of other health care services. Therefore, we explored factors associated with acupuncture treatment for LBP and the relation of acupuncture with other health care services.     

Phosphatidylinositol 3'-kinase/AKT signaling is activated in medulloblastoma cell proliferation and is associated with reduced expression of PTEN.

PURPOSE: Medulloblastomas represent the most frequent malignant brain tumors of childhood. They are supposed to originate from cerebellar neural precursor cells. Recently, it has been shown that Sonic Hedgehog-induced formation of medulloblastoma in an animal model is significantly enhanced by activation of the phosphatidylinositol 3'-kinase (PI3K) signaling pathway. EXPERIMENTAL DESIGN: To examine a role for PI3K/AKT signaling in the molecular pathogenesis of human medulloblastoma, we did an immunohistochemical study of the expression of Ser473-phosphorylated (p)-AKT protein in 22 medulloblastoma samples: All samples displayed p-AKT expression. To investigate if an activated PI3K/AKT pathway is required for medulloblastoma cell growth, we treated five human medulloblastoma cell lines with increasing concentrations of the PI3K inhibitor LY294002 and analyzed cellular proliferation and apoptosis. The antiproliferative effect could be antagonized by overexpressing constitutively active AKT. As the activation of PI3K/AKT signaling may be associated with alterations of the PTEN gene located at 10q23.3, a chromosomal region subject to frequent allelic losses in medulloblastoma, we screened PTEN for mutations and mRNA expression. RESULTS: Proliferation of all of the medulloblastoma cell lines was dependent on PI3K/AKT signaling, whereas apoptosis was not prominently affected. Allelic loss was detected in 16% of the cases. One medulloblastoma cell line was found to carry a truncating mutation in the PTEN coding sequence. Even more important, PTEN mRNA and protein levels were found to be significantly lower in medulloblastomas compared with normal cerebellar tissue of different developmental stages. Reduction of PTEN expression was found to be associated with PTEN promoter hypermethylation in 50% of the tumor samples. CONCLUSIONS: We conclude that activation of the PI3K/AKT pathway constitutes an important step in the molecular pathogenesis of medulloblastoma and that dysregulation of PTEN may play a significant role in this context.     

Valproic Acid prolongs survival time of severe combined immunodeficient mice bearing intracerebellar orthotopic medulloblastoma xenografts.

PURPOSE: To develop novel orthotopic xenograft models of medulloblastoma in severe combined immunodeficient mice and to evaluate the in vivo antitumor efficacy of valproic acid. EXPERIMENTAL DESIGN: Orthotopic xenografts were developed by injecting 10(3) to 10(5) tumor cells from four medulloblastoma cell lines (D283-MED, DAOY, MHH-MED-1, and MEB-MED-8A) into the right cerebellum of severe combined immunodeficient mice. Animals were then examined for reproducibility of tumorigenicity, cell number-survival time relationship, and histopathologic features. Tumor growth was monitored in vivo by serially sectioning the xenograft brains at 2, 4, 6, and 8 weeks postinjection. Valproic acid treatment, administered at 600 microg/h for 2 weeks via s.c. osmotic minipumps, was initiated 2 weeks after injection of 10(5) medulloblastoma cells, and treated and untreated animals were monitored for differences in survival. Changes in histone acetylation, proliferation, apoptosis, differentiation, and angiogenesis in xenografts were also evaluated. RESULTS: Tumorigenicity was maintained at 100% in D283-MED, DAOY, and MHH-MED-1 cell lines. These cerebellar xenografts displayed histologic features and immunohistochemical profiles (microtubule-associated protein 2, glial fibrillary acidic protein, and vimentin) similar to human medulloblastomas. Animal survival time was inversely correlated with injected tumor cell number. Treatment with valproic acid prolonged survival time in two (D283-MED and MHH-MED-1) of the three models and was associated with induction of histone hyperacetylation, inhibition of proliferation and angiogenesis, and enhancement of apoptosis and differentiation. CONCLUSION: We have developed intracerebellar orthotopic models that closely recapitulated the biological features of human medulloblastomas and characterized their in vivo growth characteristics. Valproic acid treatment of these xenografts showed potent in vivo anti-medulloblastoma activity. These xenograft models should facilitate the understanding of medulloblastoma pathogenesis and future preclinical evaluation of new therapies against medulloblastoma.     

Hirntumoren bei Kindern und Jugendlichen

Every year, around 380 children younger than 16 years are diagnosed in Germany with a brain tumor. Different types of brain tumors are found in children compared to adults. Diagnosis is often delayed in spite of presentation with characteristic symptoms. Thus, unspecific, persistent symptoms should be followed up with further diagnostics. Since the 1980s, multimodal therapeutic regimens have been developed systematically by the Society for Pediatric Oncology and Hematology in the context of treatment optimization trials. Neurosurgery, chemotherapy and radiation are applied according to the histology, stage of metastasis, and age of the children. Currently, 80–90% of children diagnosed with a brain tumor in Germany are treated within the framework of the ‘treatment network HIT’. The principle aims are improved survival and quality of life, the reduction of therapy-associated toxicity and late effects, and better diagnostic and therapeutic standards. In this article, typical clinical symptoms, diagnostic recommendations and treatment strategies are described.     

Hirntumoren bei Kindern und Jugendlichen

Every year in Germany, around 380 children younger than 16 years of age are diagnosed with a brain tumor. Compared with adults, different types of brain tumors are found in children. The diagnosis is often delayed despite presentation with characteristic symptoms. Nonspecific persistent symptoms must be followed with further diagnostics. Since the 1980s, multimodal therapeutic regimens have been developed systematically by the Society for Pediatric Oncology and Hematology (GPOH) in the context of treatment optimization trials. Neurosurgery, chemotherapy, and irradiation are applied according to the histology, stage of metastasis, and age of the child. Currently, 80–90% of the children diagnosed with brain tumors in Germany are treated according to the respective trial in the context of the treatment network HIT. The principle aims are improved survival and quality of life, reduction of therapy-associated toxicity and late effects, and better diagnostic and therapeutic standards. In this article, typical clinical symptoms and diagnostic recommendations are described, and the structure of the HIT treatment network is illustrated.     

Nasogastric tube feedings in children with high-risk cancer: a pilot study

PURPOSE: To avoid the cost and complications of total parenteral nutrition (TPN), this study was initiated to determine the feasibility of administrating nasogastric tube feedings in children receiving intensive chemotherapy (CTX) or bone marrow transplantation (BMT). PATIENTS AND METHODS: Seventeen children (aged 2 to 19 years) were entered into the study. Continuous nasogastric feedings of a glutamine-supplemented elemental diet were administered during CTX and at the time of rehospitalization for fever, neutropenia, and mucositis. RESULTS: Fourteen children were treated with CTX and 3 with BMT. Enteral tube feedings were administered for 216 days; each patient received a mean of 12.7 days. The tubes were generally well tolerated, and there were no instances of sinusitis or epistaxis. Six children received TPN in addition to enteral feedings. The hospital charges for the enteral feedings were $25,348, compared to $112,299 for the same number of days of TPN. CONCLUSIONS: Nasogastric tube insertion and enteral tube feedings in children receiving intensive CTX or BMT can be accomplished with minimal complications and significant cost savings when compared to TPN.