Antitumor effect of lysine-isopeptides

Isopeptides (ε-peptides) of lysine, with a given Mw and low polydispersity (10–400 units), were synthesized to study the relationship between their chemical structure and biological effect. The designed compounds were of high purity, low polydispersity and high stereochemical purity. The effect of the compounds was tested on a human erythroleukemia cell line (K-562) and on four transplantable mouse tumors (L1210 lymphoid leukemia, P38 macrophage derived tumor, Ehrlich ascites carcinoma, Lewis lung tumor /LLT/). In case of the L1210 and P388 tumors and the Ehrlich carcinoma, survival of the animals was used as an indicator of the effect. In case of the Lewis lung tumor, the number and size of metastases in the lung and/or liver of treated and untreated mice were used as indicators. The polymers of polymerisation degree 80–120 (Mw 10.2–15.4 KD) showed the strongest antiproliferative effect both on K562 cells and the tumors growing in vivo. This effect was manifest with a significantly higher survival rate as compared to the control (L1210, P38, Ehrlich ascites), furthermore, by a decrease in the number and size of liver and lung metastases (LLT)

Protective effects of D-Trp6-luteinising hormone-releasing hormone microcapsules against cyclophosphamide-induced gonadotoxicity in female rats.

The possible protective effect of an agonist of luteinising hormone-releasing hormone (LH-RH) against the ovarian damage caused by cyclophosphamide was investigated in rats. D-Trp6-LH-RH microcapsules were injected once a month for 3 months, in a dose calculated to release 25 micrograms day-1. Control animals received the injection vehicle. Sixty days after the first injection of microcapsules, cyclophosphamide was given at a loading dose of 50 mg kg-1 followed by 5 mg kg-1 day-1 for 30 days, while the treatment with D-Trp6-LH-RH was continued. When the ovaries were examined 3 months and 5 months after discontinuation of treatment, a significant reduction in the total number of follicles (P less than 0.01) was found in non-pretreated animals given cyclophosphamide. This reduction affected mainly follicles larger than 100 microns. An irreversible disintegration and destruction of granulosa cells was also observed in this group. In animals pretreated with D-Trp6-LH-RH, administration of cyclophosphamide caused no reduction in the number and diameter of follicles. Thus, the treatment with D-Trp6-LH-RH microcapsules before and during chemotherapy prevented the ovarian injury inflicted by cyclophosphamide. The suppression of gonadal function by LH-RH analogues could be possibly utilised for the protection of the ovaries against damage caused by cytotoxic drugs

The Relation of Occupational Identity, and Family Background Variables in a Hungarian Sample of Emerging Adults

Background: In the last few decades, identity formation has been postponed until the mid or late twenties (ARNETT 2000). ARNETT calls this specific period between 19–27 emerging adulthood. According to WATERMAN (1999), some family variables can foster or hinder the process of identity development. In our study, we investigate the relation of parenting styles described by BAUMRIND (1991), two-parent or one-parent family backgrounds, and occupational identity. Among the dimensions of identity, we will focus on occupational identity, since it has great importance in this period of life. Method: Besides demographic variables and data regarding the participants’ family background, we used the Melgosa Occupational Identity Scale (OIS), Parental Authority Questionnaire (PAQ). The sample consisted of 220 19–29-year-old emerging adults. Results: According to our hypothesis, identity diffusion and moratorium show a slightly negative correlation with age. Regarding occupational identity, it seems significant whether the person could or could not find a job in accordance with their qualifications: the moratorium is higher among those who could not, while foreclosure and identity achievement is higher among those who found a job in their professional field. Regarding family background, it seems that children of divorced parents do now show higher rates of less adaptive identity statuses, but foreclosure is higher among children raised in two-parent families. Conforming to our expectations, we found that permissive parenting is related to identity diffusion, while interestingly, both the father’s and the mother’s authoritative parenting is related to foreclosure

Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers

Insulin-like growth factors (IGFs) I and II are implicated in progression of various tumours including colorectal carcinomas. To interfere with the production of IGFs, we treated male nude mice bearing xenografts of HT-29 human colon cancer with various potent growth hormone-releasing hormone (GH-RH) antagonists. Twice daily injections of antagonist MZ-4-71, 10 μg intraperitoneally or 5 μg subcutaneously (s.c.) resulted in a significant 43–45% inhibition of tumour growth. Longer acting GH-RH antagonists, MZ-5-156 and JV-1-36 given once daily at doses of 20 μg s.c. produced a 43–58% decrease in volume and weight of cancers. Histological analyses of HT-29 cancers demonstrated that both a decreased cell proliferation and an increased apoptosis contributed to tumour inhibition. GH-RH antagonists did not change serum IGF-I or IGF-II levels, but significantly decreased IGF-II concentration and reduced mRNA expression for IGF-II in tumours. In vitro studies showed that HT-29 cells produced and secreted IGF-II into the medium, and addition of MZ-5-156 dose-dependently decreased IGF-II production by about 40% as well as proliferation of HT-29 cells. Our studies demonstrate that GH-RH antagonists inhibit growth of HT-29 human colon cancers in vivo and in vitro. The effect of GH-RH antagonists may be mediated through a reduced production and secretion of IGF-II by cancer cells. © 2000 Cancer Research Campaig

Assessment of subacute genotoxic and histopathological effects of a food flavour ingredient, 4-ethylbenzaldehyde (EBA) on zebrafish (Danio rerio) model

Modern food industry widely uses a variety of flavour and fragrance materials. One of the most used compound groups is the aldehydes. The benzaldehyde, also known as artificial almond oil, is one of the most commonly used flavouring in food industry nowadays. The effects of this compound on different species are well known, a lot of toxicological information can be found in the literature. 4-ethylbenzaldehyde is also a member of aldehyde group, the physical properties are similar to benzaldehyde and also has almond scent. Unlike benzaldehyde, it has no chemical safety assessment according to its chemical safety sheet, and only one experiment can be found on its effects on vertebrates. This compound can also be found at the group of flavours and fragrances. The aim of this study was to examine the subacute DNA and tissue damaging effects of EBA. The genotoxic effects of EBA in zebrafish were evaluated by using micronucleus assay. Significant increase in the micronucleus frequency had been described for all tested concentrations. Alterations were found in the liver of the fish group treated with 11 mg l–1 EBA for 21 days

Effectiveness and cost-effectiveness of body psychotherapy in the treatment of negative symptoms of schizophrenia - a multi-centre randomised controlled trial

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