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Biomedical subjects

M Picardo

Publications and source records attributed to M Picardo.

At least 127 records · Page 7Linked to original sources

Effect of dicarboxylic acids on Harding-Passey and Cloudman S91 melanoma cells in tissue culture.

Clinically, dicarboxylic acids have a cytotoxic effect on the abnormally hyperactive and malignant epidermal melanocyte, and diacids from C8 to C13 have been shown to inhibit mitochondrial oxidoreductases. Here, their effect on the growth kinetics and ultrastructure of murine melanoma cells in culture is examined. Cultures of Harding-Passey and Cloudman S91 melanoma cells were exposed to single doses of the disodium salts of C12, C9, and C6 (which does not significantly inhibit mitochondrial enzymes) dicarboxylic acids at concentrations of 10(-3) M to 10(-1) M. With C12 and C9, viability and cell proliferation over 3 days were significantly affected by concentrations greater than 10(-2) M. With exposure to C6 at 10(-1) M and to medium to which NaCl was added to produce equal osmolarity, the effect was much less. Electron microscopy of cells exposed to C9 at 10(-1) M for 1 h and 6 h revealed massive swelling of mitochondria with destruction of cristae, but plasma and nuclear membranes and membranes of endoplasmic reticulum were intact. Similar damage was not seen with C6 at 10(-1) M nor with equiosomolar NaCl. The results confirm (1) the cytotoxicity of dicarboxylic acids for malignant melanocytes, and (2) that the mitochondrion is a prime target for their action.

Adipates↗

Ultrastructural observations on the effect of azelaic acid on normal human melanocytes and a human melanoma cell line in tissue culture.

Azelaic acid has been shown clinically to have a cytotoxic effect on the abnormally active and malignant human melanocyte, but it has no apparent effect upon normal melanocytes. This difference in reactivity between normal and abnormal cells in vivo is further examined here in vitro. The disodium salt of azelaic acid (C(9)2Na) was added to pure and mixed cultures of normal human melanocytes and to cultured human melanoma cells, at 10(-3) M, 10(-2) M, 5 X 10(-2) M, and 10(-1) M for 1 and 6 h. Control cultures and cultures exposed to the same concentrations of the disodium salt of adipic acid (C(6)2Na) were also examined. No damage to cells of any line was observed with diacids at 10(-3) M or 10(-2) M up to 6 h. At 5 X 10(-2) M some mitochondria of melanoma cells appeared swollen. With C(6)2Na at 10(-1) M for I and 6 h, minimal swelling of mitochondria was observed in some cells of all lines. Pure normal melanocytes and melanocytes of mixed cultures exhibited greater swelling of mitochondria with 10(-1) M C(9)2Na at 1 and 6 h, but the mitochondria of the malignant melanocytes were massively swollen with destruction of cristae. Plasma and nuclear membranes and membranes of rough endoplasmic reticulum were intact, but Golgi membranes exhibited vesiculation. These results provide further evidence that azelaic acid damages the human malignant melanocyte and that one of its targets is the mitochondrion. Damage to normal melanocytes, found here, may be due to the fact that, in culture, they are more active than in intact epidermis.

Cell Line↗

Contact dermatitis to Alstroemeria.

A study was carried out on 50 workers in a floriculture centre to evaluate the incidence of contact dermatitis to Alstroemeria. 3 subjects gave positive reactions to aqueous and ethanolic extracts of cut flowers, stems and leaves. By column chromatography, the allergen was isolated and its chemical structure identified as 6-tuliposide A by proton magnetic resonance and carbon-13 magnetic resonance. Only 6-tuliposide A was isolated from cut flowers, and this gave positive reactions when patch tested at 0.01%; a-methylene-gamma-butyrolactone at 10(-5) (v/v) was positive in the same 3 subjects. Other lactones (gamma-methylene-gamma-butyrolactone, alantolactone, isoalantolactone) were negative at all concentrations used.

Adult↗

Antimitochondrial effect of saturated medium chain length (C8-C13) dicarboxylic acids.

In isolated rat liver mitochondria, respiration was competitively inhibited by medium chain length (C8 to C13) dicarboxylic acids to different extents: the higher the number of carbon atoms up to C12, the greater the inhibition. In particular, experiments on submitochondrial particles showed that the competitive inhibition concerned the following enzymes: NADH dehydrogenase, succinic dehydrogenase and reduced ubiquinone: cytochrome c oxido-reductase. These results tend to confirm the suggestion that the melanocytotoxic effect of dicarboxylic acids, which are also competitive inhibitors of tyrosinase, may be primarily due to an antimitochondrial effect rather than being tyrosinase-dependent.

Adenosine Triphosphate↗

Beneficial effect of 15% azelaic acid cream on acne vulgaris.

Patients treated with azelaic acid (15%) cream for chloasma reported simultaneous improvement of acne lesions within the treated areas. This prompted an open study of its effect in cases of acne without chloasma. One hundred patients with acne vulgaris were treated for 3-9 months by twice-daily application of the cream with significant improvement in every case.

Acne Vulgaris↗

Metabolism of straight saturated medium chain length (C9 to C12) dicarboxylic acids.

A method utilizing thin-layer chromatography, high performance liquid chromatography, and mass spectrometry was developed for the quantification of C9, C10, C11, and C12 dicarboxylic acids in serum, urine, and feces of human volunteers and rats after oral administration of the acids. The method allowed good resolution and measurement of the dicarboxylic acids at nanogram levels. In humans, excretion was independent of the dosage; about 60% of C9, 17% of C10, 5% of C11, and 1% of C12 were excreted in the urine during the first 12 hours after administration. The concentration of the acids in serum peaked between 2 and 3 hours. Excretion was also independent of dosage in rats. About 2.5% of C, 2.1% of C10, 1.8% of C11, and 1.6% of C12 were excreted in the urine over a period of 5 days. The serum concentration and the urinary excretion of the diacids reached a maximum at the second day after the oral dose. In both humans and rats, the dicarboxylic acids found in serum and urine were 2, 4, or 6 carbon atoms shorter than the corresponding administered diacid. This indicates that there was beta-oxidation of the ingested diacids to some extent. The administration of [1,9-14C]azeliac acid and of [10,11-3H]dodecandioic acid confirmed the occurrence of beta-oxidation, and led to elucidation of the fate of the ingested diacids that were not excreted as such in the urine.

Administration, Oral↗

Hormonal regulation of glycogen metabolism in hepatocyte suspensions isolated from chicken embryos.

1. A method is described for efficient and rapid isolation of viable hepatocyte suspensions from chick embryos in the last few days of incubation. 2. Although qualitatively similar, quantitative differences exist in the hormonal control of glycogen metabolism between embryonic and hatched chicks. 3. Glucagon and adrenaline activate glycogenolysis. 4. Insulin did not inhibit basal or glucagon-stimulated glycogenolysis. 5. Phenylephrine (an alpha-adrenergic agonist), angiotensin and vasopressin, all of which activate glycogen breakdown in rat liver through a Ca2+-dependent mechanism, were without effect on chick embryo hepatocytes.

Angiotensins↗

Circulating immune complexes in Behçet's syndrome: purification, characterization and cross-reactivity studies.

The C1q-binding assay was performed on 30 sera from patients with Behçet's syndrome and circulating immune complexes were found in 46%. Circulating immune complexes were isolated and purified from the sera of two patients by immunoadsorption on a column of polymethylmetacrylate beads coated with C1q and then labelled with 125I. In double immunodiffusion these purified immune complexes were found to contain IgG, C1q, C1s and C3. Anti-IgG activity was not detectable in the purified immune complexes while specific cross-reactivity was found in a solid-phase radioimmunoassay with the majority of the sera of behçet's syndrome.

Antigen-Antibody Complex↗

Action of glutamic acid and of some glutamate analogues on the molluscan central neurones.

The effects of L-glutamic acid and of some glutamate analogues have been studied on the central nervous system of the snail Heobania vermiculata, using conventional electrophysiological techniques. The glutamate H-response had the mean equilibrium value of -(57 +/- 4) mV and was associated with a Cl- conductance change. The D-response to glutamate application showed an involvement of sodium ions. Aspartate was agonist of glutamate action and displayed similar equilibrium value of the H-response, whereas quisqualate H-response was 'non-invertible'.

Animals↗

Effects of fluorophore structure and hydrophobicity on the uptake and metabolism of fluorescent lipid analogs.

Cellular transport and metabolism of fatty acids are integral components of lipid metabolism, but the mechanisms and regulation involved are poorly understood. A variety of commercially available fluorescent analogs of fatty acids, are potentially useful probes for the study of lipid metabolism by such techniques as cell sorting and fluorescence microscopy. We have screened a series of fluorescent fatty acids to identify analogs that would reliably simulate the metabolic behavior of natural fatty acids; i.e., similar kinetics of transport, of intracellular movement, and of metabolic fate. The metabolic behavior of these analogs was compared with those of some naturally occurring fatty acids in HepG2 cells, which are a good model of some aspects of hepatic function. Fluorescent analogs containing polar fluorophores yielded the lowest rates of cellular uptake and conversion to acylated lipid products. Similarly, fluorescent analogs with the fluorophore located near the carboxylic acid group were poorly metabolized. Fatty acid analogs containing anthracene or pyrene at the n-terminus of the acyl chain were the most extensively incorporated into cellular lipids. The types and amounts of labeled lipid products formed from these analogs and from natural fatty acids were similar. Pyrene-labeled analogs have spectral properties that can be measured fluorometrically at very low concentrations. Therefore, we compared the cellular metabolism of 12-(1-pyrenyl)dodecanoic acid with those of palmitic and oleic acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗

Lipids of the sperm plasma membrane: from polyunsaturated fatty acids considered as markers of sperm function to possible scavenger therapy.

This article is, in part, a review of present knowledge regarding the lipid metabolism of the sperm cell and the lipid composition of the sperm plasma membrane. It is also a summary of our research on this topic, reporting published and unpublished data. The article tries to cover both basic and clinical research. Sperm cells use lipid metabolic pathways for the production of part of their energy. The double leaflets of the membrane are not simply a passive, bilayer, lipidic film in which the receptors receive their molecular specific signals, but are a very specialized structure. Complete maturation of the lipids of the sperm cell membrane is reached after passage of the spermatozoon through the epididymis. A specific composition of phospholipids and a significant concentration of polyunsaturated fatty acids (PUFA) have been shown to be present in sperm membranes. Plasmalogen is a special kind of phospholipid found exclusively in spermatozoa and other cells with the capacity to react promptly to stimuli. In addition, we have found a high concentration of the n-3 PUFA family in the sperm membrane. Seminal plasma has a highly specialized scavenger system that defends the sperm membrane against lipoperoxidation. Various pathologies and systemic predisposition can lead to an antioxidant/pro-oxidant disequilibrium. Clinical trials with natural scavengers could be a useful research area in which to seek a treatment for these pathologies. Of the natural scavengers, glutathione has been shown to restore the physiological constitution of PUFA in the cell membrane under certain conditions.

Biomarkers↗