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Biomedical subjects

S Moro

Publications and source records attributed to S Moro.

At least 55 records · Page 3Linked to original sources
PubMed1997

1-Thiopsoralen, a new photobiologically active heteropsoralen. Photophysical, photochemical and computer aided studies.

1-Thiopsoralen (7H-thieno[3,2-g]benzofuran-7-one) 1, a lead compound of a series of heteropsoralens, was investigated. The electronic transitions involved were studied. Fluorescence quantum yield is very low, while laser flash photolysis showed that the triplet state is practically the sole transient of 1. Fluorescence quantum yield (phi F) and triplet lifetime (tau F) as well as triplet quantum yield (phi T) and lifetime (tau T) were determined. The production of singlet oxygen was also evaluated by photophysical measurements. Photophysical data suggest that DNA photobinding of 1, owing to short fluorescence lifetime value and high triplet quantum yield, occurs likely through triplet mechanism. Interactions between 1 and DNA were studied both in the ground and the excited state. In the ground state 1 undergoes intercalation inside duplex DNA. This fact is also supported by molecular modeling studies. By UVA-light activation 1 photobinds covalently to DNA forming mono and diadducts. The furan side 1-thymine monoadduct, isolated from DNA photomodified by thiopsoralen, shows a cis-syn stereochemistry, in agreement with quantum mechanics studies. Compound 1 photobinds also with linolenic acid, component of lecithins, giving a C4-cycloaddition, and supporting that this compound also induces photolesions at the level of cell membrane, like psoralen. Compound 1 exhibits strong skin-phototoxicity.

Animals↗
PubMed1995

The natural history of untreated anterior cruciate tears in recreational athletes.

A followup study was performed to elucidate the natural course of acutely torn anterior cruciate ligaments in recreational athletes. Fifty-six consecutive patients had arthroscopy within 2 weeks of their initial injuries; however, no surgery was done on the torn anterior cruciate ligament. Twenty anterior cruciate ligament and medial collateral ligament combined ruptures occurred. Patient ages ranged from 14 to 50 years old (mean, 28.9 years). Followup periods ranged from 2 to 10 years (mean, 5 years 6 months). Through examination with the KT-1000 arthrometer, side-to-side differences of anterior translation of the tibia of > or = 3 mm in 72% patients at reexamination were seen. Eight of 46 patients had mild osteoarthritic changes of Grade 1 visible on radiographs, but only 1 patient reported knee trouble. Nine patients had repeat injuries, 3 of whom had late reconstructions and 4 late meniscectomies. Functional scores averaged 95 +/- 6.5 points. Activity scores averaged 4.8 +/- 1.6 points. Operative management for the medial structure did not improve the stability better than nonoperative management. Anterior translation and functional scores of patients with medial meniscectomies showed significant differences from those of other patients. Anterior cruciate ligament reconstruction for recreational athletes should be considered when the patients have reparable meniscal tears, and meniscal repairs should be performed simultaneously.

Adolescent↗
PubMed1991

[VCAP combination chemotherapy of multiple myeloma in the aged].

A comparative study between patients aged over 65 (elderly group) and those under 65 (non-elderly group) was performed to determine the therapeutic efficacy of combination chemotherapy with vincristine, cyclophosphamide, Adriamycin and prednisolon (VCAP) for untreated multiple myeloma as both induction and maintenance therapy. The subjects selected were 38 patients with untreated myeloma who presented over the 7.5 years from 1982 to 1989 (June), consisting of 14 aged over 65 and 24 aged under 65. According to the classification of Durine and Salmon, 3 and 11 patients of the elderly group were stage II and III cases, respectively, while the numbers were 8 and 16 in the non-elderly group. The results defined by Imamura's criteria showed a 61.3% (9/14) partial remission rate in the elderly group and a 66.7% (17/24) rate in the non-elderly group. The 50% survival was 43 months in the elderly group and 65.5 months in the non-elderly group, with no significant difference between the groups. Thus, VCAP therapy for the induction of remission and maintenance for multiple myeloma therapy resulted in satisfactory prolongation of life in both groups, with a low incidence of the adverse reactions.

Adult↗
PubMed1978

Isolation and characterization of a Golgi-rich fraction from the Harding-Passey mouse melanoma.

Golgi-rich fraction was isolated from Harding-Passey mouse melanoma by centrifugation through the discontinuous sucrose density gradient and its properties were compared with those of the same fraction isolated from rat liver. The specific activity of UDP-galactose: N-acetylglucosamine galactosyltransferase was 35 times higher in the melanoma Golgi fraction than in the melanoma homogenate and was a half that in the rat liver Golgi fraction. The specific activities of marker enzymes for other subcellular components such as 5'-nucleotidase, acid phosphatase and glucose-6-phosphatase in the melanoma Golgi fraction were all one-third those in the melanoma homogenate. Electron micrographs of the negatively-stained Golgi fractions of melanoma and liver revealed the presence of a system of tubules, vesicles and plate-like center regions which are known as components of Golgi apparatus. Tyrosinase activity was found to be present in this fraction of mouse melanoma, but its specific activity was lower than that in the rough or smooth surface membrane fraction or in the melanosome fraction.

Animals↗
PubMedDate not supplied

Structurally related nucleotides as selective agonists and antagonists at P2Y1 receptors.

The P2Y1 receptor responds to adenine nucleotides and is present in platelets, heart, smooth muscles prostate, ovary, and brain. A selective antagonist may be useful as an antithrombotic agent. We have analyzed the binding site of this G protein-coupled receptor using ligand design, site-directed mutagenesis, and homology modeling based on rhodopsin. We have designed and synthesized a series of deoxyadenosine 3',5'-bisphosphate derivatives that act as antagonists, or, in some cases with small structural changes, as agonists or partial agonists. The 2-position accommodates Cl or thioethers, whereas the N6-position is limited to Me or Et. 2'-Substitution with OH or OMe increases agonist efficacy over 2'-H. Using molecular modeling of the binding site, the oxygen atoms of the ribose moiety were predicted to be non-essential, i.e. no specific H-bonds with the receptor protein appear in the model. We have, therefore, substituted this moiety with carbocylics, smaller and larger rings, conformationally constrained rings, and acyclics, with retention of affinity for the receptor. With simplified pharmacophores we are exploring the steric and electronic requirements of the receptor binding site, and the structural basis of receptor activation.

Binding Sites↗
PubMedDate not supplied

Molecular modeling studies of human A3 adenosine antagonists: structural homology and receptor docking.

Molecular modeling studies were conducted on various chemically diverse classes of human A3 adenosine receptor antagonists (hA3ANTs), such as adenines, xanthines, triazoloquinazolines, flavonoids, thiazolopyridines, 6-phenyl-1, 4-dihydropyridines, and 6-phenylpyridines. Using a combination of ab initio quantum mechanical calculations, electrostatic potential map comparison, and the steric and electrostatic alignment (SEAL) method, a general pharmacophore map for hA3ANTs has been derived. Based on the proposed pharmacophore map, we hypothesize that the receptor binding properties of different A3 antagonist derivatives are due to recognition at a common region inside the receptor binding site and, consequently, a common electrostatic potential profile. A model of the human A3 receptor, docked with the triazoloquinazoline reference ligand CGS 15953 (9-chloro-2-(2-furyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine), was built and analyzed to help interpret these results. All other antagonist structures were docked inside the receptor according to the results obtained through the steric and electrostatic alignment (SEAL) approach using the structure of CGS 15953 as a template. The receptor model was derived from primary sequence comparison, secondary structure predictions, and three-dimensional homology building, using rhodopsin as a template. An energetically refined 3D structure of the ligand-receptor complex was obtained using our recently introduced cross-docking procedure (J. Med. Chem. 1998, 41, 1456-1466), which simulates the ligand-induced reorganization of the native receptor structure.

Animals↗
PubMedDate not supplied

Ribose modified nucleosides and nucleotides as ligands for purine receptors.

Molecular modeling of receptors for adenosine and nucleotide (P2) receptors with docked ligand, based on mutagenesis, was carried out. Adenosine 3',5'-bisphosphate derivatives act as selective P2Y1 antagonists/partial agonists. The ribose moiety was replaced with carbocyclics, smaller and larger rings, conformationally constrained rings, and acyclics, producing compounds that retained receptor affinity. Conformational constraints were built into the ribose rings of nucleoside and nucleotide ligands using the methanocarba approach, i.e. fused cyclopropane and cyclopentane rings in place of ribose, suggesting a preference for the Northern (N) conformation among ligands for P2Y1 and A1 and A3ARs.

Animals↗
PubMedDate not supplied

[Bilateral synovial chondromatosis of the first metatarsophalangeal joint: a case report. ].

Synovial chondromatosis is a rare pathology of unknown aetiology. It originates from the chondroid metaplasia of the connective tissue of the synovial membrane. Consequently, cartilaginous nodules develop in the affected joints, first calcifying and then ossifying. The bursae mucosae, the vaginae tendinis and the para-articular connective tissue are less frequently affected. The most common locations of this pathology are the knee, the hip, the shoulder, the elbow and the ankle. The small joints are rarely affected, even less the bilateral involving of joints, above all of hand or foot, is exceptional. In a clinical and radiological valuation, it is difficult to distinguish synovial chondromatosis from osteoarthritis and from degenerative arthopathies in general. A sure diagnosis can be obtained only by means of a histological examination. We here report a case of synovial chondromatosis bilaterally located on the first metatarsophalangeal joint. Clinical and radiological features were similar to those of hallux rigidus, a typical and peculiar metatarsophalangeal joint pathology. The diagnostic suspicion arose during surgery, and was subsequently confirmed by histological examination. During the following visits, the patient did not present any painful symptomatology.

Aged↗
PubMedDate not supplied

[Leishmaniasis outbreak in Cancha Larga, Chaco, Argentina].

A leishmanioasis outbreak is reported among the inhabitants of an endemic area for this disease located in Cancha Larga, Chaco in Argentina. Frotis and biopsy confirmed that 11.8% of the whole population was affected. They were all treated with meglumine antimonate.

Adult↗