Uncommon use of intermittent glucose administration for infrequent non-epileptic paroxysmal events in GLUT1-DS.

The ketogenic diet is the treatment of GLUT1 deficiency syndrome that provides an alternative energy source for the brain. However, there are some limitations, including compliance issues as well as patients who do not respond to the ketogenic diet. We report the case of two patients that were not on any particular diet.

Accumulation of hydroxyspermidine in red blood cells, a potential index of tumor proliferation rate.

It has previously been demonstrated that during Lewis Lung carcinoma growth, red blood cell spermidine levels increase concomitantly with tumor volume. If [14C] putrescine or 2-methylputrescine are administered, [14C] spermidine and methylspermidine, respectively, accumulate in red blood cells in proportion with the tumor volume. In the present work the metabolic transformation of 2-hydroxyputrescine, a natural derivative of putrescine, to hydroxyspermidine, was studied in tumor bearing mice.

Pretherapeutic erythrocyte polyamine spermine levels discriminate high risk relapsing patients with M1 prostate carcinoma.

Background: Androgen deprivation is currently the standard treatment for patients with metastatic prostate carcinoma. Few reliable prognostic markers are able to select, at diagnosis, patients who will respond favorably and durably to hormone ablation. Circulating polyamines, markers of cell proliferation that are elevated in prostate carcinoma, have been evaluated as a prognostic tool.

Observations with an S-adenosylmethionine decarboxylase inhibitor in rats with prostatic adenocarcinoma.

CGP 48664A (2-(4-aminoiminomethyl)-2,3-dihydro-1H-inden-1-ylidene dihydrochloride, CAS 149400-88-4) is a new potent inhibitor of S-adenosylmethionine decarboxylase with antitumor properties. In view of the eminent clinical problems in the treatment of non hormone dependent prostatic cancer, the antiproliferative potency of this compound was tested in Dunning MAT-LyLu rat prostatic adenocarcinoma. The compound proved inefficient in preventing the growth of this tumor, even at a near toxic dose.

Red blood cell polyamines, anaemia and tumour growth in the rat.

In rats with Mat Lylu prostatic carcinoma, significant changes in blood composition and red blood cell (RBC) characteristics were observed. Anaemia, characterised by a decrease in the number of RBC and the reduction of haemoglobin and the iron content in plasma, was correlated with tumour size and the accumulation of spermidine and spermine in the RBC. In large tumours, spermidine levels were increased by 8-fold over normal value.

In vivo, synergestic inhibition of MAT-LyLu rat prostatic adenocarcinoma growth by polyamine deprivation and low-dose cyclophosphamide.

Polyamine deprivation in vivo produces significant tumor growth inhibition of the hormone-resistant, metastatic Dunning Mat-LyLu murine prostatic carcinoma. In order to produce a cytotoxic effect in addition to the cytostatic effect of polyamine deprivation, various chemotherapy regimens, combined with drug-containing polyamine-deficient chow (DC-PDC), were assessed. Triple chemotherapy combining methotrexate, cyclophosphamide and vindesine; and monochemotherapy with high-dose cyclophosphamide (90 mg.

Determination of erythrocyte polyamines as a predictive method in tumour diagnosis. An animal study with chemically induced tumours.

There have been numerous attempts in the past to use polyamine determinations in body fluids for tumour diagnosis. Since spermidine (Spd) and spermine (Spm) are mainly transported in blood by erythrocytes, this study was concerned with the diagnostic possibilities of red blood cell (RBC) polyamine determinations. In tumour-grafted animals we observed that RBC polyamine levels correlated with the tumour mass progression and increased before the tumour was palpable.

Differential recognition of free and covalently bound polyamines by the monoclonal anti-spermine antibody SPM8-2.

The reactivity of an anti-spermine MAb (SPM8-2) toward polyamines either free or bound to a solid surface was investigated using equilibrium dialysis and ELISA methods. When polyamines were covalently linked to hydrophilized microtiter plates using carbodiimide, the MAb SPM8-2 reacted both with spermine and spermidine, with a higher affinity for the latter, but did not show any reactivity towards bound putrescine. In contrast, the MAb SPM8-2 reacted with all three polyamines bound to the microtiter plates with glutaraldehyde, with an affinity in the order: putrescine > spermidine > spermine.

Erythrocyte polyamine levels: an indication of successful engraftment of bone marrow in children.

We studied the evolution of erythrocyte polyamine levels after 17 autologous bone marrow transplants (BMT) in 16 children with malignant diseases. We found that the time to the end of aplasia (0.5 x 10(9) granulocytes per liter) could be divided into 2 distinct periods.

[The involvement of polyamines in the malignant proliferative process. The anticancer effect of polyamine deprivation].

The fact that tumors require polyamines for growth has been repeatedly demonstrated. In vivo polyamines are available both from endogenous (intracellular biosynthesis) and exogenous sources (food and intestinal microflora). We investigated in rats grafted with Mat-Lylu prostatic adenocarcinoma the distribution between tumor and tissues of orally administered (14C) putrescine (Pt).

Procedural memory and Parkinson's disease.

A detailed analysis of the mnestic deficits associated with Parkinson's disease (PD) contributes to explaining the cognitive disorders and their well documented consequences. This study was designed to show that, in PD declarative as well as procedural memory is severely impaired. Three tests designed to explore this aspect of mnestic functioning were proposed to a group of 16 parkinsonian patients whose motoricity was controlled: inverted reading, braille reading, sound form association.

Alterations in intestinal uptake of putrescine and tissue polyamine concentrations in tumor-bearing rats.

Intestinal absorption of putrescine and tissue metabolism of polyamines were investigated in rats grafted with the rapidly growing Mat-Lylu prostatic tumor. These animals exhibited a dramatic 21% decrease in weight and protein, but not DNA, content of their intestinal mucosa, relative to healthy rats reared under similarly controlled nutritional conditions. No significant variation in the specific activities of intestinal brush-border membrane enzymes was observed, however, suggesting a comparable differentiation state of intestinal cells exists in both groups.

[Involvement of polyamines in malignant proliferative processes: antineoplastic effects of a polyamine deficiency].

The fact that tumors require polyamines for growth has been repeatedly demonstrated. In vivo polyamines are available both from endogenous (intracellular biosynthesis) and exogenous sources (food and intestinal microflora). We investigated in rats grafted with Mat-Lylu prostatic adenocarcinoma the distribution between tumor and tissues of orally administered [14C]putrescine (Pt).

Internalization of metformin is necessary for its action on potentiating the insulin-induced Xenopus laevis oocyte maturation.

In this study, metformin (N, N1 dimethylbiguanide) was found to potentiate insulin-induced Xenopus laevis oocyte maturation, a phenomenon of transition from late G2 to M phase of the cell cycle. These cells also accumulated exogenous metformin (130 +/- 6.5 nmol/oocyte).

Polyamine deprivation: a new tool in cancer treatment.

The fact that tumors require polyamines for growth has been demonstrated in vitro and in vivo and widely reported. This finding led to the use of polyamine biosynthetic enzymes as targets for antitumor drug design. Highly efficient in vitro selective inhibitors of ornithine decarboxylase such as DFMO do not produce important antitumoral effects in vivo, due to the ability of tumor cells to uptake extracellular polyamines.

Erythrocyte polyamines and prognosis in stage D2 prostatic carcinoma patients.

We studied 43 patients with newly diagnosed, untreated, stage D2 prostatic carcinoma, and correlated the initial performance status, hemoglobin, prostate specific antigen levels, tumor Gleason grade, extent of disease on the bone scan, and erythrocyte spermidine and spermine levels with progression. Three patients died of unrelated causes and were excluded from the study, 16 remained in remission with a mean 28 +/- 11 months of followup and 24 had progression (18, or 75%, of whom died of the cancer) with a mean 12 +/- 9 months of followup (p < 0.05 for followup) after initiation of hormonal therapy.

Polyamine transport regulation by calcium and calmodulin: role of Ca(2+)-ATPase.

The study was conducted on human leukemia (K 562) cells to characterize the mechanisms implicated in the regulation of the polyamine spermidine (Spd) transport process. The antagonists of calmodulin, trifluoperazine (TFP), W-7 (N-[6-aminohexyl]-5-chloro-1-naphthelenesulfonamide), or mellitin inhibited significantly polyamine Spd uptake in these cells. The translocation of calmodulin towards plasma membrane and a concomitant decrease in its contents in cytosol were directly correlated with the time course increases similar to that of Spd uptake, indicating that calmodulin is recruited towards plasma membrane during the Spd transport process.

Polyamine deprivation stimulates natural killer cell activity in cancerous mice.

It has recently been established that the total blockade of all endogenous and exogenous sources of polyamines by a drug containing polyamine deficient chow (DC-PDC+) could inhibit tumor growth in vivo and increase the antitumoral efficacy of chemotherapy drugs. We show here that polyamine deprivation obtained with DC-PDC+ not only influences tumor development via reduction of polyamine concentrations in the tumor itself but, in addition, stimulates cells of the non-specific immune system specialized in tumor cell killing. We report that mice grafted with the 3LL carcinoma present a dramatic decrease in the cytotoxic activity of their natural killer (NK) cells.

The effects of structural analogs of putrescine on proliferation, morphology and karyotype of glioblastoma cells in culture.

In a previous study, we identified regions on the surface of tumor cells which act as acceptor sites for putrescine (Put) and studied the competition between structural analogs of Put (N,N'-tetramethyl-alpha,omega-diaminoalkanes) and Put bound to latex microspheres. A chain of four to seven carbons was necessary for inhibition of Put-latex binding to the cell surface of human glioblastoma (U251) cells. We show here that under the experimental conditions, N,N'-tetramethyl-1,4-butanediamine and N,N'-tetramethyl-1,7-heptanediamine exhibit an antitumor effect.

Polyamines and prostatic carcinoma: clinical and therapeutic implications.

The erythrocyte polyamines, spermidine and spermine, are known proliferation markers. The authors present their experience with polyamines and prostatic carcinoma. 229 patients with prostatic carcinoma had polyamine erythrocyte determination at diagnosis.

Polyamine deprivation enhances antitumoral efficacy of chemotherapy.

We reported previously that polyamine deprivation by feeding a polyamine deficient diet combined with gastrointestinal tract decontamination and polyamine oxidase inhibition considerably enhanced the antitumoral effect of DFMO, a selective inhibitor of ornithine decarboxylase. The combination of polyamine deprivation and administration of well established cytotoxic drugs was expected to improve further the antitumoral effect of polyamine deprivation in Lewis lung carcinoma grafted in mice. Simultaneous treatment, i.

Characterization of metformin transport system in NIH 3T3 cells.

The biochemical properties of the metformin transport system were studied in NIH 3T3 cells. 14C-metformin uptake appeared to be a sodium dependent process. Iso-osmotical replacement of Na+ by choline chloride in the assay medium resulted in a decrease of metformin uptake.

Depletion in nuclear spermine during human spermatogenesis, a natural process of cell differentiation.

Polyamines (PA), polycations present in all mammalian cells, are essential for cell proliferation and differentiation. In vitro, PA are known to bind to DNA with a high affinity. In vivo, the intimate association of endogenous PA with highly condensed chromatin has been reported.

Proton NMR spectroscopy of plasma lipoproteins in the experimental Lewis lung carcinoma.

Plasma and fractionated lipoproteins from 40 Lewis Lung Carcinoma grafted mice were tested from the first day up to the fatal issue by biochemical analyses and water suppressed 1H NMR spectroscopy. We have confirmed first, that the 1H NMR spectra of plasma lipoproteins are modified by the tumoral state and could provide a useful marker of the disease as long as they are used for individual follow-up with appropriate spectral parameters. Using fractionated lipoproteins we have demonstrated secondly, that the observed spectral modifications do not result from a specific cancer lipoprotein but from quantitatively modified ratio between Very Light Density Lipoproteins and High Density Lipoproteins.

Protein kinase C inhibitor (H-7) potentiates antiproliferative effects of a polyamine biosynthesis inhibitor.

In this study, a protein kinase C inhibitor, H-7, was found to potentiate the antiproliferative effects of difluoromethyl ornithine (DFMO), inhibitor of the polyamine biosynthesis, on NIH 3T3 and 3T3/SV40 cells in culture. Incubation of the cells with DFMO inhibited the cell growth, whereas the addition of polyamine spermidine to these cells restored the normal rate of cell proliferation with the fact that these cells took up the polyamine from the extracellular medium to compensate the intracellular needs. The addition of H-7 to both the 3T3 and 3T3/SV40 cells, inhibited the cell proliferation, though the level of inhibition was always lower than in those treated with the DFMO alone.