Cobalt chloride induces neurite outgrowth in rat pheochromocytoma PC-12 cells through regulation of endothelin-2/vasoactive intestinal contractor

We investigated whether endothelin-2/vasoactive intestinal contractor (ET-2/VIC) gene expression, upregulated by hypoxia in cancer cells, was associated with differentiation in neuronal cells. RT-PCR analysis, morphological observations, and immunostaining revealed that CoCl2, a hypoxic mimetic agent, at 200 microM increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene, and induced neurite outgrowth in PC-12 rat pheochromocytoma cells. These effects induced by 200 microM CoCl2 were completely inhibited by the antioxidant N-acetyl cysteine at 20 mM. In addition, CoCl2 increased the level of intracellular reactive oxygen species (ROS) at an early stage. Furthermore, interleukin (IL)-6 gene expression was upregulated upon the differentiation induced by CoCl2. These results suggest that expression of ET-2/VIC and ET-1 mediated by ROS may be associated with neuronal differentiation through the regulation of IL-6. When the cells were treated with 500 microM CoCl2 for 24 hr, however, ET-2/VIC gene expression disappeared, IL-6 gene expression was downregulated, and necrosis was subsequently induced in the PC-12 cells.     

Effect of postoperative chemotherapy on the serum alpha-fetoprotein level in hepatoblastoma

Purpose

It is generally accepted that postoperative chemotherapy does not affect the serum alpha-fetoprotein (AFP) level. The authors report on 3 patients who supposedly showed chemotherapy-related changes in their AFP levels after operation.

Methods

This study included 3 patients with hepatoblastoma (1 case of PRETEXT III and 2 cases of PRETEXT IV).

Results

One patient with PRETEXT III underwent a complete tumor resection, and the postoperative AFP level decreased until it reached the normal range. However, he consistently exhibited a transient, 2- to 3-fold increase in the AFP after each course of chemotherapy for 3 courses. The chemotherapy regimen had to be stopped because of drug-induced encephalopathy, but he has been followed up for 5 years without any evidence of recurrence, and his AFP level has also remained stable and in the normal range. Two patients with PRETEXT IV, who underwent a curative tumor resection, also showed similar chemotherapy-related changes in AFP levels. Both of these cases were observed only after the administration of routine postoperative chemotherapy instead of administering further high-dose chemotherapy. The AFP level remained stable for 17 months and 7 months after the cessation of chemotherapy in 2 cases, respectively.

Conclusions

Regarding the postoperative chemotherapy of hepatoblastoma, we have to pay close attention to both the AFP status during chemotherapy as well as the absolute AFP level.     

Hexachlorobenzene, a dioxin-like compound, disrupts auditory function in rat

Hexachlorobenzene (HCB) is a dioxin-like compound widely distributed in the environment. In this study, we investigated the effects of HCB on the cochlea. Conscious free-moving rats were given HCB per os daily for 4 weeks at doses of 0.16, 4 or 16 mg/kg in olive oil, whereas the control group received olive oil only. The effects of HCB were evaluated at various time intervals, by measuring auditory nerve acoustic thresholds and plasma thyroid hormone concentration by radioimmunoassay. Histological evaluation involved surface preparation and scanning electron microscopy observations of cochlear hair cells. At a dose of 0.16 mg/kg, HCB induced no loss of acoustic sensitivity, whereas at 4 mg/kg, it induced cochlear sensitivity deficits at the mid-frequencies (2-16 kHz) with complete recovery once treatment was stopped. At a dose of 16 mg/kg, permanent threshold shifts were observed at all frequencies tested (from 1 to 32 kHz). Morphological studies showed no cochlear hair cell loss or alteration of stereocilia. HCB treatment reduced circulating thyroxine concentrations. Thyroidectomy had no effect on cochlear sensitivity in control animals. Thus, HCB is a potent oto-toxicant, and its ototoxicity may be independent of its thyroidal effects.     

Toxocariasis: under-estimated disease. Report of 9 cases

Toxocariasis or visceral larva migrans is a parasitosis due to the migration in the human organism of animal ascarid larvae. Its importance is under-estimated and the reported tunisian cases are rare. We report nine cases of toxocariasis, noted between January of 2000 to March of 2002, in the laboratory of parasitology-mycology in La Rabta Hospital. They were six children and three adults. The clinical forms are varied: ophthalmologic form (5 cases), general syndrome (1 case), oedema (1 case) and hypereosinophilia (2 cases), and confirmed serologically by the presence of anti Toxocara canis antibody using ELISA test. Visceral larva migrans should be kept in mind to avoid severe forms such as ophthalmologic forms.     

Accelerated dynamic MR imaging with a parallel imaging technique for hypervascular hepatocellular carcinomas: usefulness of a test bolus in examination and subtraction imaging

PURPOSE: To assess the impact of the accelerated dynamic MR imaging (ADMRI) approach using parallel imaging for detecting hypervascular hepatocellular carcinomas (HCCs) and to evaluate the usefulness of a test bolus in examination and subtraction imaging in this setting. MATERIALS AND METHODS: Thirty patients with 135 HCCs underwent ADMRI using a two-dimensional gradient-recalled echo sequence with parallel imaging. Seventeen patients were evaluated without a test bolus and 13 patients with a test bolus. The detectability of HCCs was calculated between the groups with and without a test bolus. ADMRI was evaluated regarding the signal-to-noise ratio (SNR) of the lesion and the liver, the contrast-to-noise ratio (CNR) of the lesion vs. the liver, and the feasibility of subtraction images. RESULTS: ADMRI with and without a test bolus had almost equal sensitivity (92.5% and 92.6%). No significant difference was seen in the SNR of lesions and the CNR of lesions vs. livers between both groups. With a test bolus, ADMRI could depict the peak enhancement of nodules on the 2nd or 3rd dynamic phases and optimized the timing of peak lesion enhancement. Subtraction images could be obtained regarding minimal slice misregistration. CONCLUSION: ADMRI had high detectability of HCCs with and without a test bolus.     

Placento-thyroidal relationship in normal pregnancy.

Estimations of serum HCT, HTSH, T4, T3, PBI, ETR, Triosorb, TBG-binding capacity, BMR and urinary total estrogen were made simultaneously in 160 women in normal pregnancy. TRH stimulation tests were made in 20 cases in each trimester of pregnancy. HCT was detectable even in early pregnancy, tending to increase gradually toward the terminal stage of pregnancy as serum thyrotrophin bioactivity showed. On the other hand, serum TSH level measured by radio-immunoassay remained essentially the same throughout the course of pregnancy as in the nonpregnant state, moreover, it was suggested by the TRH stimulation test that pituitary TSH secreting function of pregnant women was similar to that of the non-pregnant. These findings suggest that thyroid hyperfunction during pregnancy which is shown by progressively increased T3, T4, and PBI may not be due to high estrogen-high TBG binding capacity-low free thyroxinenegative feed back-high TSH secretion but to HCT originating from placenta. In spite of thyroid hormone increase, it is true that the clinical picture of hyperthyroidism is not manifest among normal pregnant women, and ETR remained within the non-pregnant range throughout the course of pregnancy. We have also demonstrated that Triosorb decreased progressively. This may be interpreted to be due to the increase of TBG binding capacity which is increased progressively and binds more of free thyroxine during pregnancy. Such a change in TBG binding capacity is well known to be caused by the effect of estrogen which is progressively increased during pregnancy. In a word, it is possible to say that there is a placento-thyroidal system in pregnancy; HCT elevates thyroid function and TBG increased by estrogen carries thyroid hormone to target organ.     

High-dose carboplatin–irinotecan–temozolomide is an effective salvage chemotherapy for relapsed or refractory neuroblastoma

There is no clear consensus on the most effective treatment for relapsed/refractory high-risk neuroblastoma (NB). We retrospectively assessed seven NB patients with relapsed/refractory disease who received high-dose carboplatin–irinotecan–temozolomide (HD-CIT). Five of seven patients showed favorable therapeutic response (complete remission or partial remission). Regarding toxicity, the cytopenia period tended to prolong when more than three cycles were repeated, but nonhematological toxicities were controllable with general supportive care. Due to its antitumor efficacy and well-tolerated nonhematologic toxicity, HD-CIT is a promising salvage chemotherapy for relapsed/refractory NB. However, it is important to pay attention to the exacerbation of hematological toxicity when repeating the regimen.     

cDNA cloning and sequence analysis of Xenopus laevis preproendothelin-1

Endothelin (ET)-like immunoreactivity has been observed not only in mammals, but also in amphibians. The biological actions of ET are similar in amphibians and mammals, and amphibian ET-related receptors have been cloned and characterized. The cDNA sequences of mature and precursor forms of ET-related peptides, however, have not been reported in any amphibian until now. To identify the ET-related peptides, we screened the Xenopus laevis intestine cDNA library using the rapid amplification of cDNA ends method and cloned cDNAs encoding preproendothelin-1. The deduced amino acid sequence of X. laevis preproendothelin-1 comprises 223 amino acids, including a putative signal sequence of 19 amino acids, a mature ET-1 of 21 amino acids, as well as big ET-1 and ET-1-like sequences. X. laevis ET-1 is identical to mammalian ET-1 as well as ET-1 peptide, recently purified from the stomach of the European green frog, Rana ridibunda. This is the first report describing the cDNA encoding preproendothelin-1 in an amphibian species.