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Biomedical subjects

Miriam Rossi

Publications and source records attributed to Miriam Rossi.

13 recordsLinked to original sources
PubMed2006

Mitochondria are primary targets in apoptosis induced by the mixed phosphine gold species chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I) in melanoma cell lines.

Based on previous evidence indicating a selective cytotoxic activity of the mixed phosphine gold complex chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I) for melanoma cells, we investigated the cellular bases of its antiproliferative effect in a panel of human melanoma cell lines (JR8, SK-Mel-5, Mel-501, 2/60, 2/21 and GRIG). The drug consistently induced a dose-dependent inhibition of cell growth, with IC50 values ranging from 0.8 to 2.3 microM and, when tested under the same experimental conditions, its cytotoxic activity was higher than (from 2- to 5-fold) or comparable to that of cisplatin as a function of cell lines. The ability of the gold complex to activate programmed cell death was assessed in JR8 and 2/60 cells, and a dose-dependent increase in cells with an apoptotic nuclear morphology was observed in both cell lines (up to 40 and 66% of the overall cell population, for JR8 and 2/60 cell lines, respectively). Such an apoptotic response was mediated by a dose-dependent loss of mitochondrial membrane potential, cytochrome c and Smac/DIABLO release from mitochondria into cytosol and enhanced caspase-9 and caspase-3 catalytic activity. A reduced or completely abrogated expression of the anti-apoptotic proteins c-IAP1, XIAP and survivin in drug-treated cells was also observed. Overall, results from the study indicate that chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I) markedly inhibits melanoma cell growth by inducing mitochondria-mediated apoptosis and suggest it as a good candidate for additional evaluation as an anticancer agent against melanoma.

Antineoplastic Agents↗
PubMed2006

Synthesis and anticonvulsant activity of new N-1',N-3'-disubstituted-2'H,3H,5'H-spiro-(2-benzofuran-1,4'-imidazolidine)-2',3,5'-triones.

Thirteen new N-1',N-3'-disubstituted-2'H,3H,5'H-spiro-(2-benzofuran-1,4'-imidazolidine)-2',3,5'-triones were synthesized and their pharmacological activity determined with the objective to better understand their SAR for anticonvulsant activity. The anticonvulsant effects of these compounds were evaluated by standard pentylenetetrazol (scPTZ test) and maximum electroshock seizure (MES test) models in mice. Most of the compounds showed ability to protect against the pentylenetetrazol-induced convulsions. Compound 3o (the N-1'-p-nitrophenyl, N-3'-ethyl derivative) in the N-1'-aryl, N-3'-alkyl disubstituted series exhibited maximum activity with ED(50) of 41.8 mg/kg in scPTZ convulsion model.

Animals↗
PubMed2006

Dietary treatment in adult-onset type II glycogenosis.

Eight patients with adult-onset type II glycogenosis (GSD II), all carrying the IVS1-13T<G mutation, were treated with high-protein isocaloric diet for 3 years. We evaluated the usefulness of this approach through the assessment of the skeletal muscles (by manual muscle testing, quantitative isokinetic exercise, and muscle MRI) and the respiratory function (by spirometry). Three patients with mild or moderate disease severity refused the diet and were still monitored for comparison: they showed clinical (2 patients) or clinicoradiological (1 patient) progression of muscle weakness, while respiratory function remained unchanged. Among the patients accepting the dietary treatment, muscle strength remained unchanged, as did the degree of fatty infiltration and atrophy as assessed by muscle MRI; respiratory function worsened in 2/5 patients with severe baseline respiratory dysfunction. High-protein diet may stabilize disease progression at the skeletal muscles, but does not produce significant clinical improvements; moreover, the usefulness of this approach in patients with severe respiratory disease seems questionable.

Adult↗
PubMed2005

Synthesis, spectroscopy (IR, multinuclear NMR, ESI-MS), diffraction, density functional study and in vitro antiproliferative activity of pyrazole-beta-diketone dihalotin(IV) compounds on 5 melanoma cell lines.

Novel 4-acylpyrazolon-5-ato-dihalotin(IV) complexes, [Q2SnX2], (X = F, Cl, Br or I); HQ = HQ(CHPh2) (1,2-dihydro-3-methyl-1-phenyl-4-(2,2-diphenylacetyl)pyrazol-5-one), HQ(Bn) (1,2-dihydro-3-methyl-1-phenyl-4-(2-phenylacetyl)pyrazol-5-one) or HQ(CF3,py) (4-(2,2,2-trifluoroacetyl)-1,2-dihydro-3-methyl-1-(pyridin-2-yl)pyrazol-5-one) have been synthesized and characterized by spectroscopic (IR, 1H, 13C, 19F and 119Sn NMR, electrospray ionisation mass spectrometry (ESI-MS)), analytical and structural methods (X-ray and density functional theory). 119Sn chemical shifts depend on the nature of the halides bonded to tin. Isomer conversion, detected in solution by NMR spectroscopy, is related to the acyl moiety bulkiness while the cis(Cl)-cis(acyl)-trans(pyrazolonato) scheme is found in the solid state. The in vitro antiproliferative tests of three derivatives on three human melanoma cell lines (JR8, SK-MEL-5, MEL501) and two melanoma cell clones (2/21 and 2/60) show dose-dependent decrease of cell proliferation in all cell lines. The activity correlates with the nature of the substituent on position 1 of pyrazole, decreasing in the order pyridyl>Ph>>methyl. The activity for (Q(CF3,py))2SnCl2 on the SK-MEL-5 cell line is IC50 = 50 microM.

Animals↗
PubMed2004

Structural basis for antioxidant activity of trans-resveratrol: ab initio calculations and crystal and molecular structure.

From the experimental crystal structure and ab initio calculations on resveratrol and its derivatives, structural features of mechanistic importance are described. The molecular structure reveals the relative coplanarity of the trans-stilbene skeleton, and the molecular packing in the solid state shows an extensive hydrogen bond network that elucidates the flip-flop motion of the three hydroxyl groups that alternately form and break H bonds with each of the neighboring phenolic oxygens. The dynamic behavior provoked by the alternation of hydrogen bond formation and breaking can result in the ready mobility of up to three hydrogen atoms per resveratrol molecule that can be transferred to reactive oxidants that are rich in electron density. In addition, theoretical studies confirm the planarity of resveratrol as well as for half of the molecule of a condensation dimeric derivative of resveratrol, trans-sigma-viniferin. Furthermore, these studies show the p-4'-OH group to be more acidic compared to the other two m-OH groups. These features correlate with the biological activity of resveratrol as an antioxidant and support earlier studies showing H-atom transfer to be the dominant mechanism by which phenolic antioxidants intercept free radicals.

Antioxidants↗
PubMed2004

Prevalence and correlates of Chlamydia infection in Canadian street youth.

PURPOSE: To determine the prevalence and correlates of Chlamydia trachomatis in Canadian street youth. METHODS: A cross-sectional study of street youth between the ages of 15-24 years was conducted over a 9-month period in seven large urban centers across Canada. Youth were recruited through "drop-in" centers, outreach work, and mobile vans in each city. Information was collected through a nurse-administered questionnaire. Youth were asked to provide urine to test for chlamydia trachomatis by polymerase chain reaction. Separate logistic regression models were run for males and females controlling for age. RESULTS: The prevalence rate of chlamydia was 8.6% in 1355 youth (95% CI = (7.1%, 10.1%)). Higher prevalence rates were found in females than in males (10.9% vs. 7.3%, respectively) and in Aboriginal youth than in non-Aboriginal youth (13.7% vs. 6.6%, respectively). Four variables were associated with increased risk of chlamydia infection in females: Aboriginal status; self-perceived risk; having no permanent home; and having been in foster care. One predictor of chlamydia for males was having had a social worker. CONCLUSIONS: A high prevalence of chlamydia was found in this vulnerable population in comparison to other Canadian youth. Having been in foster care and having had a social worker were found to have a strong association with chlamydia.

Adolescent↗
PubMed2004

Muscle MRI in adult-onset acid maltase deficiency.

We report the spectrum of muscle involvement on magnetic resonance imaging in 11 patients with a molecularly confirmed diagnosis of adult-onset acid maltase deficiency at different clinical stages. Muscle magnetic resonance imaging showed a selective progressive pattern of muscle involvement with a constant involvement of the adductor magnus and semimembranosus at the early stage of the disease and a later fatty infiltration of the long head of the biceps femoris, semitendinosus and of the anterior thigh muscles. In the advanced phases a selective sparing of sartorius, rectus, and gracilis muscles and peripheral portions of the vastus lateralis was also evident. Muscle strength and magnetic resonance imaging findings were positively correlated. The results suggest that muscle magnetic resonance imaging may provide valuable diagnostic guidance for the assessment of accurate selective muscular involvement in acid maltase deficiency and may help monitor the progression of the disorder. Further control studies in a larger cohort are needed to evaluate the specificity of these findings.

Adult↗
PubMed2004

Antitumor titanium compounds.

Most anticancer titanium compounds act against tumors in the gastrointestinal tract. Activity towards breast, lung and skin (melanoma) cancers is shown by some as well. Among their appealing properties is that they do not show common side effects of widely used cytostatic agents such as emesis, alopecia or bone marrow impairment. These features make titanium compounds interesting for combined therapy and further study. This review focuses on two drugs that reached clinical trials, namely, titanocene dichloride and budotitane. We try to integrate the biological fate of the related Ti-cyclopentadienyl and Ti-beta-diketonato families of drugs, delineating the structure-activity relationship. We also discuss novel related species with increased solubility for improved drug delivery and some potentially useful polynuclear compounds.

Antineoplastic Agents↗
PubMed2003

Antitumor activity of the mixed phosphine gold species chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I).

The title compound has been designed for antitumor activity based on structural features of related known antitumor gold agents, that is, gold-monophosphine and gold-diphosphine derivatives. It is a gold complex that contains both types of phosphine ligands, thus suggesting a possible synergistic action. The results of a single crystal X-ray structure determination of this molecule show the metal surrounded by 3 P atoms and one Cl anion in a distorted tetrahedral arrangement. The chloro anion, however, is weakly bound to the metal and so the species shows ionic character. The P NMR study, performed in solution, confirms the structural features observed in the solid and, in addition, indicates partial formation of other known gold(I)-diphosphine antitumor agents. The ionic character and strong Au-P bonds of this novel gold(I) species are similar to those of the most active antitumor gold compounds so far studied. The former feature contributes to solubility in biological fluids, and the latter prevents fast biomolecular attack. In addition, the title compound is less lipophilic, a feature recently correlated to lower liver toxicity. The title compound shows in vitro antitumor activity in the two initial National Cancer Institute protocols against human tumors. In the first screening, a unique dose (0.10 mM) of the title compound reduced cell growth of MCF7 (breast cancer), NCI-H460 (lung cancer), and SF-268 (Central Nervous System cancer-CNS) to 5, 8, and 11%, respectively. In the second protocol a 60-cell line panel was analyzed with the title compound concentration in the 0.1 mM-0.01 microM range. The highest activity was for the breast tumor cell line MCF7 with a LC(50) less than 0.01 microM. LC(50) values in the micromolar range were obtained for 29 cell lines. With the exception of leukemia, these micromolar activities were observed in at least one cell line for each subgroup tumor (non small lung, colon, CNS, melanoma, renal, prostate, breast, and ovarian). The leukemia inactivity was unexpected, as all antitumor gold(I) phosphine compounds in the literature described thus far are active. Melanoma was the most sensitive subgroup screened (five out of seven cell lines).

Antineoplastic Agents↗
PubMed1997

A Short Pb.Pb Separation in the Polymeric Compound Bis(pyrrolidinecarbodithioato)lead(II) and a Conformational Pathway Interconversion for the "Pb(II)S(4)" Framework.

The X-ray structure of bis(pyrrolidinecarbodithioato)lead(II), Pb(II)(pdtc)(2), C(10)H(16)N(2)S(4)Pb, shows the metal to be on a crystallographic 2-fold axis. The primary Pb-S bonds are equal, 2.89 Å; this is a unique feature of this compound compared to other Pb(II) dithiocarbamate structures. The crystal structure consists of polymeric Pb(pdtc)(2) units stacked along the c axis in two antiparallel columns; successive Pb(pdtc)(2) units are staggered. There are weaker Pb-S bonding interactions with the unit above (secondary Pb-S bonds) such that the coordination polyhedron formed by the eight S atoms bound to the Pb atom is a distorted square antiprism. Successive antiprisms share the pyramidal base, and the Pb.Pb distance between neighboring Pb(pdtc)(2) units is 3.886(1) Å. We analyze the structures of other PbS(4) compounds and find that the Pb lone pair is important in defining their geometry. The large variety of Pb configurations results from peripheral changes in the ligand. This is due to a compromise between the efficient use of space in the crystal and the tendency of lead to have different coordination numbers. These configurations can be described by a pathway of conformational interconversion from a 4-sided pyramidal geometry to an octahedral system. The title compound crystallizes in the orthorhombic space group Pccn with z = 4; cell constants are a = 13.839(14) Å, b = 14.058(16) Å, c = 7.763(6) Å.

Journal Article↗