Effect of alfa-difluormethylornithine on Anastrepha fraterculus (Diptera, Tephritidae) ovary size / Efeito da alfa-difluorometilornitina nas dimensões dos ovários em Anastrepha fraterculus (Diptera, Tephritidae)

Ovarian sizes (length and width) were measured in young females of Anastrepha fraterculus (Wiedemann) (Diptera, Tephritidae) subjected or not to the inhibitor α -difluormethylornithine (α -DFMO). The most effective concentration of α -DMFO used was 50 mM and the ovarian measurements (length and width) of the treated females were smaller than those of females not treated with α -DMFO. These data may suggest some relationship between ornithine decarboxylase (ODC) and sexual maturation in A. fraterculus.

As dimensões dos ovários (comprimento e largura) foram mensuradas em fêmeas jovens da Anastrepha fraterculus (Wiedemann) (Diptera, Tephritidae) submetidas ou não ao inibidor α -difluormetilornitina (α -DFMO). A concentração mais efetiva de α -DMFO utilizada foi 50 mM e as medidas (comprimento e largura) das fêmeas tratadas com o inibidor foram menores que as fêmeas não tratadas com inibidor α -DMFO. Estes dados podem sugerir uma relação entre ornitina descarboxilase (ODC) e maturação sexual em A. fraterculus.

Effect of alpha-difluoromethylornithine on the expression of ODC mRNA in the cortex and hippocampus in rats after cerebral ischemia reperfusion / 中南大学学报(医学版)

OBJECTIVE@#To explore the mechanism of alpha-difluoromethylornithine (DFMO) inhibiting ODC activity in the cortex and hippocampus in rats.@*METHODS@#Forty male rats was randomly divided into ischemal control group and DFMO pretreatment group. DFMO was given intravenously half an hour before global cerebral ischemia, and expression of ODC mRNA was measured by comparative reverse transcription-polymerase chain reaction (RT-PCR) in the cortex and hippocampus in rats after 2, 4, 6 h and 8 h of reperfusion. The variations of the expression of ODC mRNA were studied in the DFMO pretreatment group and the ischemal control group respectively.@*RESULTS@#After 2, 4 and 6 h of reperfusion, the expression of ODC mRNA in the cortex and hippocampus in the pretreatment group was lower than that in the ischemia control group significantly (P 0.05).@*CONCLUSION@#DFMO suppressed the expression of ODC mRNA after different lengths of reperfusion following 10-minute global cerebral ischemia in rats and it may be one of the ways for DFMO to inhibit ODC activity.

Polyamines Regulate Growth Factor-Induced Protein Phosphorylation in MCF-7 Human Breast Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Growth factors stimulate protein phosphorylation resulting in transmission of mitogenic signals. In breast cancer, protein kinases and their substrate proteins are importnat in cell proliferation and phathogenesis. Polymine is known as a mediator of stimuli-induced proliferation in many cell systems. In the present study, we report the importance of polyamines in protein phosphorylation in MCF-7 human breast cancer cells. MATERIALS AND METGODS: Protein phosphorylation study was done by incubating cells in the DMEM containing [gamma-(32)P]-ATP. Quantitation of phosphorylation was analysed by fluorescene image analyzer. Tyrosine phosphorylation was detected by anti-phosphotyrosine antibody. Shc was detected by radioimmunoprecipitation and Western blotting. RESULTS: E2, TGF-alpha, and EGF enhanced the protein phosphorylation in very similar pattern. Among those proteins, 67 kDa protein was most strongly phosphorylated. But the most prominent tyrosine phosphoprotein was 52 kDa protein. DFMO at 5 mM strongly inhibited the phosphorylation of the most proteins. Externally added polyamine could recover the inhibitory effect of DFMO in protein phosphorylation. Among the 5 major tyrosine phosphoproteins, 52 and 46 kDa proteins appeared to be Shc proteins. CONCLUSION: Polyamines modulate signal transduction in relation with estrogen receptor and EGF receptor through multiple steps of protein phosphorylations. Tyrosine phosphorylation of Shc proteins were most significantly influenced by polyamines in growth factor-stimulate breast cancer cell proliferation.

Effect of alpha-difluoromethylornithine on growth characteristics and expression of ALT-04ag gene of human lung carcinoma cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effect of polyamine biosynthesis inhibition on growth characteristics of human lung carcinoma cells and its correlation with the expression of human lung carcinoma associated antigen ALT-04ag gene.</p><p><b>METHODS</b>The gene expression was detected by RT-PCR and immunocytochemical tests. The cell growth characteristics were studied by cell growth curves, morphological observation, FCM analysis and DNA electrophoresis.</p><p><b>RESULTS</b>Human lung squamous carcinoma cells L78 treated with 5 mmol/L alpha-difluoromethylornithine (DFMO) for 5 days showed significant growth inhibition and apoptosis induction. The mRNA and protein expressions of ALT-04ag gene in the cells were downregulated, while these changes resulted from DFMO treatment were prevented by provision of DFMO along with exogenous putrescine.</p><p><b>CONCLUSION</b>The effect of polyamine biosynthesis inhibition induced by DFMO restrains the growth characteristics and promotes apoptosis of human lung carcinoma L78 cells, which is associated with down regulation of ALT-04ag gene expression.</p>

Plating densities, alpha-difluoromethylornithine effects and time dependence on the proliferation of IEC-6 cells / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To characterize the role of plating densities and alpha-difluoromethylornithine (DFMO) on the proliferation of IEC-6 cells in vitro.</p><p><b>METHODS</b>IEC-6 cells were seeded in 96-well microplates at various densities in the presence or absence of DFMO. Cells were counted and their proliferative capability was monitored Days 1 to 7 with MTT assay at an optical density of 570 nm.</p><p><b>RESULTS</b>There was a positive relationship between cell number and OD value (r = 0.954, P < 0.01). Higher plating densities (> 0.5 x 10(4) cells/well) inhibited the growth of cells on Day 2. When the density reaches 4 x 10(4) cells/well, the OD value increased gradually and reached a peak on Day 5. After that, the OD value began to fall. The growth of IEC-6 cells was limited at a low density (0.2 x 10(4) cells/well) on Day 4. DFMO caused a complete inhibition of proliferation of IEC-6 cells on Days 1 to 3.</p><p><b>CONCLUSION</b>Proliferation of IEC-6 cells is related to plating density and incubation time. It is inhibited by DFMO, but is reversible when the incubation time is prolonged.</p>

Effects of alpha-difluoromethylornithine on the Fas expression and apoptosis in Hep-2 cells

DFMO is an irreversible inhibitor of ornithine decarboxilase (ODC), the key enzyme in mammalian polyamine biosynthesis, and has been shown to induce apoptosis. In this paper, the relation between the effects of DFMO on the polyamine content, apoptotic index and Fas expression in HEP-2 cells was determined. Fas is a type I membrane protein with a molecular mass of 45 kDa, which mediates apoptosis. The results suggest that the treatment with the polyamine inhibitor DFMO induced the expression of the surface antigen Fas, which could be responsible for trigger apoptosis in these cells.

Effects of alpha-difluoromethylornithine on the cyclin A expression in Hep-2 cells

DFMO is an irreversible inhibitor of ornithine decarboxilase (ODC), the key enzyme in mammalian polyamine biosynthesis. The goal of this study was to determine the effects of DFMO on the expression of cyclin A at different stages of the cell cycle of Hep-2 cells. The cell cycle analysis, done by measuring the incorporation of thymidine in the cell DNA, revealed that DFMO produced a lower and constant level of that incorporation; this effect is probably due to the incapacity of the cells to culminate the phase S of the cell cycle. The expression of cyclin A increased in the phases S and G2 in control cells, almost disappearing in phase M. However, in DFMO treated cultures, the expression of cyclin A was increased in M and this effect remained still after 48 h treatment. We conclude that polyamines could exert an effect on the cyclin destruction mechanism, and the depletion caused by DFMO would alter this mechanism.

Fluid regulation and A.D.H. in rat oestrus cycle; the effect of difluoromethyl ornithine [demo] and oestradiol

Plasma ADH concentration have been shown to fluctuate during the oestrus cycle of the rat and following ovariectomy. Oestradiol is also known to participate in the regulation of fluid and electrolyte balance. To determine how these variations in ADH and oestradiol concentrations are related to fluid balance, studies have been carried out in the overiectomized female rats injected subcutaneously daily with oestradiol benzoate [50 [micro]g/rat] and specific inhibitor of ornithine decarboxylase [ODC]; difuormethylorithine [DEMO 20 mg/100 g.b.w] for 7 days. The animals were housed in individual metabolism cages under 12 hr dark regimen with free excess to food and water. Urine samples to determine volume were obtained and food and water intake recorded at 8:00-9:00 and 17:00-18:00 hr. Plasma samples for determination of ADH levels by radioimmunoassay were taken. In DFMO and cestradiol benzoate treated rats, food and water intake were reduced during both dark and light periods compared with vehicle treated rats. But more urine output was observed in these animals. The result of this study indicate decreased water retention in the drug treated animals as compared to the controls. The observations of this study have shown that the underlying cause of fluid retention in the cycling rat during pro-oestrus may the oestradiol dependent elevation of the ADH levels. Furthermore, this increase in ODC activity in the hypothalamic neurons is part of mechanism underlying the oestradiol induced ADH release

Alfa - difluoromethylornithine Reduced Protein Phosphorylation in MCF-7 Human Breast Cancer Cells / 대한암학회지

No abstract available.

Fluid balance: changes in cycling rats treated with difluoro-methyl-ornithine [DFMO] during the pro-oestrus.

Plasma vesopressin levels have been shown to fluctuate through out the rat oestrus cycle and following ovariectomy. To determine how these fluctuations in vesopressin are related to fluid regulations during the rat oestrus cycle. Studies have been carried out in cycling females rats using a specific inhibitor of Ornithine Decarboxylase [ODC], Di-fluoro-methyl Ornithine [DFMO 20 mg/100g body weight], the animals were housed in individual metabolism cages under 12 hours light/12 hour dark regimen with free access to food and water. Urine samples were collected to determine the osmolality and sodium concentration at 8.00 and 17.00-18.00 hours. The results of this study indicate a significant decrease in urine osmolality and sodium retention in the cycling pro-oestrus rats treated with DFMO as compared to the controls. The result of this study indicates that cause of fluid retention in the cycling rats during pro-oestrus may be the oestradiol dependent increased levels of vesopressin and the increase in the ODC activity in the Magno-cellular neurons is the part of mechanism underlying the oestradiol induced Vesopressin release

Role of endogenous polyamines in the proliferation of normal hematopoietic progenitor cells: high-proliferative potential colony-forming cells (HPP-CFC), and low-proliferative potential colony-forming cells (LPP-CFC). Studies "in vitro"

This study concerns the role of endogenous polyamines in the proliferation of normal hematopoietic progenitor cells: high-proliferative potential colony-forming cells (HPP-CFC), and low-proliferative potential colony-forming cells (LPP-CFC) in CFW/ep mouse bone marrow cells in the agar culture system. DL-a-difluoromethylornithine (DFMO) was used as a selective and irreversible inhibitor of ornithine decarboxylase which is the first limiting step in polyamine biosynthesis. The polyamines have been implicated in cell proliferation and differentiation. The results showed that DFMO significantly inhibited the formation of LPP-CFC colonies and completely inhibited the growth of the HPP-CFC colonies. Addition of exogenous putrescine at the concentration of 10(-7) M reverses the suppressive action of DFMO in both progenitor cells. At this concentration putrescine alone had no affect on the number or the size of the colonies. It was then concluded that endogenous polyamines appear to be essential for HPP-CFC proliferation and an important requirement for LPP-CFC proliferation.

Control of zoopathogenic fungi in vitro by polyamine biosynthesis inhibitors.

Effect of inhibitors of polyamine (PA) biosynthesis, alpha-difluoromethylornithine (DFMO), methylglyoxal bis (guanylhydrazone)--MGBG and bis (cyclohexylammonium) sulphate (BCHA) on mycelial growth of three clinically important fungi-Trichophyton mentagrophytes, Microsporum gypseum and Aspergillus flavus was examined in vitro. All inhibitors at concentrations 1 to 50 mM produced greater inhibition of mycelial growth in all fungi tested in a dose-dependent manner. MGBG was the most effective inhibitor, and T. mentagrophytes was the most sensitive fungus to all inhibitors followed by M. gypseum and A. flavus. The results suggested that control of fungal diseases in animals and human beings with specific inhibitors of PA biosynthesis is possible.

Alteraçöes miocárdicas em AIDS / Changes myocardial in AIDS

A síndorme de imunodeficiência adquirida (AIDS) avança progressivamente, tornando-se uma epidemia de conseqüências imprevisíveis, até o momento. Apesar disso, o conhecimento da doença e as possibilidades terapêuticas no controle das infecçöes oportunistas e também da doença de base, têm possibilitado maior sobrevida aos portadores de AIDS, propiciando que as complicaçöes cardíacas sejam cada vez mais reconhecidas nos aidéticos, já que anteriormente os pacientes sucumbiam precocemente por intercorrências infecciosas. Esta atualizaçäo se propöe a mostrar o estágio de conhecimento do envolvimento do miocárdio na AIDS, manifestado como miocardites e miocardiopatia dilatada, provocada por vários agentes infecciosos e também por açäo tóxica de drogas utilizadas para tratamento das infecçöes oportunistas ou mesmo para o controle do próprio vírus do HIV

Antiproliferative effect of difluoromethylornithine on human gastric and colorectal cancer cell lines in serum containing media / 대한암학회지

No abstract available.