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Biomedical subjects

R Anton

Publications and source records attributed to R Anton.

At least 55 records · Page 3Linked to original sources

Valproate in the treatment of acute bipolar affective episodes complicated by substance abuse: a pilot study.

BACKGROUND: Bipolar disorder is commonly complicated by comorbid substance dependence. Little is known about treatment of this important subpopulation of patients with bipolar disorder. The following study was designed to preliminary explore the use of valproate in a group of patients with comorbid bipolar disorder and substance dependence. METHOD: Nine patients with bipolar disorder, as defined by DSM-III-R, and concurrent substance dependence (five alcohol, three polysubstance abuse, one cocaine) were treated with valproate in an open-label, nonblinded trial. Subjects were followed for a mean of 16 weeks. Ratings included measures of affective state (Young Mania Rating Scale, Hamilton Rating Scale for Depression [HAM-D]) as well as substance use (Time-Line Follow-Back). RESULTS: Patients tolerated valproate well with minimal reports of side effects and no liver toxicity or increase in liver function tests noted. The mean +/- SD maintenance dose of valproate was 1583 +/- 204 mg/day. Subjects evidenced significant decreases in both depression (HAM-D score 17.8 vs. 10.4, p < or = .005) and mania (Young Mania Rating Scale score 12.0 vs. 4.9, p < or = .001) ratings by Week 4, which were sustained throughout the study period. There was a significant decrease in number of days of substance use (t = 4.7, p < or = .005) as well as the amount of substances used during the follow-up period as compared with the month before valproate treatment. CONCLUSION: While limited by the open-label, nonblinded nature of the design, this study provides preliminary evidence for the efficacy of valproate in the acute treatment of bipolar episodes complicated by concomitant substance dependence. The medication was well tolerated, and no unacceptable elevations in liver function tests were seen.

Acute Disease↗

Neural-targeted gene therapy for rodent and primate hemiparkinsonism.

Expression of the rate-limiting enzyme for catecholamine biosynthesis, tyrosine hydroxylase (TH), via retroviral and plasmid expression vectors improved the efficacy of conditionally immortalized nigral neural cells in ameliorating rodent and nonhuman primate models of Parkinson's disease through neural transplantation. No improvement in rotational behavior occurred when sham transplants or nondopaminergic transplants were performed. Transplantation of the temperature-sensitive immortalized parental nigral neural line with a TH expression vector resulted in improvement for at least 2 months. Improvement was accompanied by HPLC evidence of increased L-DOPA production and immunocytochemical evidence of TH in the transfected cells increased over that of the parental line. No tumor formation was detected. These results suggest that: (1) temperature-sensitive immortalized neural cells may be genetically engineered successfully to improve their efficacy for the treatment of parkinsonism; and (2) a change in L-DOPA production, as opposed to growth factor production or other factors, is likely to account for the observed improvement, since the parental and derived lines differ by a single gene.

Animals↗

Triterpenoid saponins from the root of Sideroxylon cubense.

Two triterpenoid saponins were isolated from the root of Sideroxylon cubense and their structures were established as 3-O-beta-D-glucopyranosyl-28-O-[alpha-L-rhamnopyranosyl(1-->3)- beta-D-xylopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-->2) beta-D-xylopyranosyl] protobassic acid and 3-O-beta-D-glucopyranosyl protobassic acid. The first, designed as sideroxyloside A, is a new natural product.

Carbohydrate Sequence↗

Mabiosides C-E: triterpenoid saponins from the bark of Colubrina elliptica.

Three novel saponins, mabiosides C-E, were isolated from the bark of Colubrina elliptica together with the known mabioside B and [alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->3)-alpha-L- arabinopyranosyl]-(1-->3)-jujubogenin. All the structures were established by spectroscopic methods.

Carbohydrate Sequence↗

Two methods for measuring carbohydrate-deficient transferrin in inpatient alcoholics and healthy controls compared.

Carbohydrate-deficient transferrins (CDTs), naturally occurring glycosylated transferrin proteins, are reported to be increased in the serum of individuals who consume large quantities of alcohol (ethanol). We compared two methods for the separation and quantification of CDT, using the same alcohol-dependent patients and age-, gender-, and race-matched controls as sources of samples for both assays. There was good correlation (r = 0.89) between the microcolumn anion-exchange chromatography/RIA (MAEC/RIA) procedure and the isoelectric focusing, immunoblotting, and laser densitometry (IEF/IB/LD) procedure. Receiver operating characteristic analysis suggested that the IEF/IB/LD procedure would perform slightly better than MAEC/RIA for the overall population. However, both assays were much more sensitive for the detection of heavy alcohol consumption in men, compared with women. Alcohol consumption in the week prior to CDT measurement correlated only weakly with the concentrations measured with either assay.

Adult↗

Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species.

The proto-oncogene bcl-2 inhibits apoptotic and necrotic neural cell death. Expression of Bcl-2 in the GT1-7 neural cell line prevented death as a result of glutathione depletion. Intracellular reactive oxygen species and lipid peroxides rose rapidly in control cells depleted of glutathione, whereas cells expressing Bcl-2 displayed a blunted increase and complete survival. Modulation of the increase in reactive oxygen species influenced the degree of cell death. Yeast mutants null for superoxide dismutase were partially rescued by expression of Bcl-2. Thus, Bcl-2 prevents cell death by decreasing the net cellular generation of reactive oxygen species.

Animals↗

Pharmacognosy of Mimosa tenuiflora (Willd.) Poiret.

A chemical investigation of the bark of Mimosa tenuiflora (Willd.) Poiret, performed in our laboratory, allowed the isolation and identification of three new triterpenoid saponins (mimonosides A, B and C), three steroid saponins (3-O-beta-D-glucopyranosyl campesterol, 3-O-beta-D-glucopyranosyl stigmasterol and 3-O-beta-D-glucopyranosyl beta-sitosterol) together with lupeol, campesterol, stigmasterol and beta-sitosterol. The three new triterpenoid saponins were subjected to in vitro biological tests (immunomodulation and proliferation) using different animal and human cells in culture. The results of these tests contribute to explain the traditional use of this plant material.

Animals↗

Expression of myc-family genes in established human multiple myeloma cell lines: L-myc but not c-myc gene expression in the U-266 myeloma cell line.

Deregulated c-myc expression, as a consequence of translocation of the c-myc gene to one of the immunoglobulin loci, appears to play an important role in the pathogenesis of several B-cell tumors, including Burkitt's lymphoma, mouse plasmacytoma and rat immunocytoma. This study investigated the expression of c-myc and 2 other members of the myc gene family, L- and N-myc, at the mRNA and protein level, and analyzed for possible rearrangements of these genes in the human counterpart to the mouse plasmacytoma--multiple myeloma (MM). Nine well-characterized MM cell lines were examined by using Northern- and Southern-blot analysis and immunoprecipitation. The c-myc gene was found to be highly expressed in most MM cell lines. The level of expression was comparable to that observed in the COLO 320 and HL-60 cell lines, carrying amplified c-myc genes, and to that of B-cell lines with a higher proliferative activity than the MM cell lines. In the U-266 MM cell line, L-myc, but no c-myc mRNA or protein, was found. The L-myc gene was expressed in both early- and late-passage U-266 cells, suggesting that the L-myc expression was not the result of the in vitro cultivation. N-myc was not expressed in any of the MM cell lines. No rearrangements of c-myc or L-myc genes were found. We thus conclude that (a) in contrast to the corresponding mouse and rat B-cell tumors, c-myc is not frequently rearranged in MM; (b) c-myc is highly expressed in most MM lines; and (c) L-myc but not c-myc is expressed in the U-266 MM cell line.

DNA, Neoplasm↗

Identity of the N-terminal sequences of the three A chains of mistletoe (Viscum album L.) lectins: homology with ricin-like plant toxins and single-chain ribosome-inhibiting proteins.

Mistletoe lectin (ML) I increases the production of cytokines by mononuclear cells and has been proposed as a useful biological response modifier in the treatment of cancer. Two other lectins, ML II and ML III, have been identified in mistletoe. We report that the N-terminal sequences of the three A chains of ML I, ML II and ML III are identical, and have interesting homology with the N-terminal sequences of the A chain of ricin-like toxins and of single-chain ribosome-inhibiting proteins. In addition, the three mistletoe lectins inhibit the growth of the human tumor cell line Molt 4, ML III being the most potent. followed by ML II and ML I. This inhibition is suppressed by addition of rabbit anti-ML I antibodies to the cultured cells. The data obtained suggest that the three lectins have amino acid sequences which show extensive homology and exert very similar biological effects. They may be derived from the same precursor.

Amino Acid Sequence↗

Interferon gamma abrogates the differentiation block in v-myc-expressing U-937 monoblasts.

Extensive studies suggest a role for the myc protooncogene family in the control of cell proliferation and differentiation in vertebrates. Previously, deregulated expression of exogenous myc genes has been shown to inhibit induced differentiation in Friend erythroleukemia (MEL) cells and in human monoblastic U-937 cells. To examine the nature of the block of phorbol 12-myristate 13-acetate-induced differentiation in v-myc-expressing U-937 cells, we have studied the effect of other inducers utilizing signal pathways distinct from phorbol 12-myristate 13-acetate (i.e., 1 alpha, 25-dihydroxycholecalciferol and retinoic acid). We show that v-myc also inhibits differentiation associated with these inducers. However, the v-myc-associated block of phorbol 12-myristate 13-acetate-, 1 alpha,25-dihydroxycholecalciferol-, and retinoic acid-induced differentiation retinoic acid-induced differentiation can be overcome by adding interferon gamma as a costimulatory factor. Costimulation with interferon gamma restores terminal differentiation, as shown by acquisition of a macrophage phenotype and an irreversible growth arrest in the G0/G1 phase of the cell cycle, but induces only limited differentiation on its own. The differentiation is accomplished without altering the expression or nuclear localization of the v-myc protein. These results argue against the widely held view that down-regulation of myc expression is a general prerequisite for terminal differentiation of hematopoietic cells and suggests that interferon gamma induces a signal(s) that circumvents the v-myc activity.

Blotting, Northern↗

Triterpenoid glycosides from the bark of Mimosa tenuiflora.

Two new saponins were isolated from Mimosa tenuiflora and their structures established as 3-O-[alpha-L-rhamnopyranosyl(1----2)-beta-D-glucopyranosyl-(1----3]-(alp ha-L- arabinopyranosyl-(1----4]-beta-D-xylopyranosyl-(1----2)]-[beta-D- xylopyranosyl-(1----4)]-beta-D-glucopyranosyl)-28-O-alpha-L-rhamnopyrano syl oleanolic acid and 3-O-[alpha-L-rhamnopyranosyl-(1----2)-beta-D-glucopyranosyl-(1----3]-(al pha- L-arabinopyranosyl-(1----4]beta-D-xylopyranosyl-(1----2)]-[beta-D- xylopyranosyl-(1----4)]-beta-D-glucopyranosyl) oleanolic acid.

Carbohydrate Sequence↗

Action of calycanthine on nervous transmission in cockroach central nervous system.

Calycanthine, the principal alkaloid of the order Calycanthaceae, has been isolated from a species of the genus Psychotria (Rubiaceae) occurring in some Pacific islands. The drug is considered as a very powerful convulsant poison but very little is known about its mechanism of action. The symptoms observed were similar to those of some neuropoisons such as strychnine. The properties of this alkaloid have been investigated on the genesis, conduction, and transmission of the nerve impulse, using giant axons of the cockroach (Periplaneta americana). Calycanthine hydrochloride (10(-5) M), which did not alter nervous conduction in pre- and post-synaptic fibers, significantly reduced the efficacy of the synaptic transmission.

Action Potentials↗

Seasonal Variations of the Flavonoid Content from Ginkgo biloba Leaves.

An HPLC method for the separation and the quantitative determination of flavonol glycosides, acylflavonol glycosides, and biflavones in crude leaf extracts from GINKGO BILOBA is described. The results, expressed in percentage of rutine, kaempferol P-coumaroyl glucorhamnoside, and bilobetin showed a higher amount of acylflavonol glycosides in buds, of flavonol glycosides in spring leaves, and of biflavones in autumn leaves.

Journal Article↗

Cytotoxic activity of Amaryllidaceae alkaloids from Crinum augustum and Crinum bulbispermum.

The cytotoxic activity of five minor Amaryllidaceae alkaloids and one flavan isolated from Crinum augustum Rox and Crinum bulbispermum Milne were tested on human leukemic Molt 4 cells. Whereas the crinine-type alkaloids (6 alpha-hydroxycrinine, powelline) and the new type augustamine did not even inhibit the growth of Molt 4 cells, the lycorine-type alkaloid (pratorinine) and the crinine-type alkaloid (6 alpha-hydroxybuphanisine) showed a moderate cytotoxic activity and the flavan (4'-hydroxy-7-methoxyflavan) showed an important cytotoxic effect.

Alkaloids↗

Effects of thiol compounds versus the cytotoxicity of valepotriates on cultured hepatoma cells.

The antagonistic activity of various thiol compounds versus the cytotoxic effects of valtrate and didrovaltrate has been evaluated on cultured hepatoma cells. Compounds with free SH groups like cysteine, mercaptoethanol, dithioerythritol, and glutathione were able to suppress the cytotoxicity of the valepotriates in a dose-dependent way, whereas compounds with blocked SH groups did not antagonize these toxic effects. The possible interactions between the valepotriates and thiol compounds are discussed.

Animals↗

New Polyindolenine Alkaloids from Calycodendron milnei.

Four new alkaloids, representing the first members of new groups of polyindolinic alkaloids, have been isolated from the aerial parts of CALYCODENDRON MILNEI along with other alkaloids. The names vatine, its stereoisomer vatine A, vatamine, and vatamidine are proposed. They are polymers of six, seven, and eight N(b)-methyltryptamine units, respectively.

Journal Article↗