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Biomedical subjects

F Orsini

Publications and source records attributed to F Orsini.

36 records · Page 2Linked to original sources

Synthesis of biologically active polyphenolic glycosides (combretastatin and resveratrol series).

(E)-3-(beta-D-Glucopyranosyloxy)-4',5-dihydroxystilbene (resveratrol 3-beta-D-glucoside, piceid), (Z)-2',3'-dihydroxy-3,4,4',5-tetramethoxystilbene (combretastatin A-1), (Z)-3'-hydroxy-3,4,4',5-tetramethoxystilbene (combretastatin A-4), (Z)-2'-hydroxy-3-4-4'-5-tetramethoxystilbene (combretastatin iso-A-4), alpha, beta-dihydro-2',3'-dihydro-2',3'-dihydroxy-3,4,4',5-tetramethoxystilb ene (combretastatin B-1), the corresponding glucosides, and related compounds have been synthesized via Wittig reactions followed by glucosylation under phase-transfer catalysis. Most of the compounds synthesized have been tested with respect to biological activity (cytostatic, cytotoxic, antimitotic, neurotoxic, antiplatelet, aggregation activity).

Antineoplastic Agents↗

Isolation, synthesis, and antiplatelet aggregation activity of resveratrol 3-O-beta-D-glucopyranoside and related compounds.

Resveratrol 3-O-beta-D-glucopyranoside (1) has been isolated from the seeds of Erythrophleum lasianthum (Caesalpinioidae, Leguminosae), a South African plant used in traditional medicine, and has shown antiplatelet aggregation activity. The synthesis of 1, related hydroxystilbenes, and their glucosides has been undertaken to provide larger quantities, for further biological evaluation, and has been accomplished via Wittig reactions followed by glucosylation under phase transfer catalysis.

Glucosides↗

Selective optical sensing of silver ions in drinking water.

A new thiocarbamate derivative is used in polymeric sensing films together with a lipophilic chromoionophore for determining Ag+ at submicromolar levels. The membrane composition has been optimized with a view to measuring concentrations of Ag+ added as a bacteriostatic agent to drinking water. The results compare well with those obtained by ICPMS.

Indicators and Reagents↗

Synthesis and cardiotonic activity of novel pyrimidine derivatives: crystallographic and quantum chemical studies.

The synthesis of ethyl or methyl 4-substituted or unsubstituted 2-(dimethylamino)-5-pyrimidinecarboxylates 10-20, which is mainly carried out by reaction of ethyl or methyl 2-[(dimethylamino)methylene]-3-oxoalkanoates with 1,1-dimethylguanidine, is described. The above esters were hydrolyzed to the relative carboxylic acids 21-30, which were decarboxylated to the corresponding 2,4-disubstituted pyrimidines 31-40. All the new synthesized pyrimidines were evaluated in spontaneously beating and electrically driven atria from reserpine-treated guinea pigs. Their effects were compared to those induced by milrinone in both atria preparations. Compound 28 (4-benzyl-2-(dimethylamino)-5-pyrimidinecarboxylic acid) was the most effective positive inotropic agent, while the corresponding methyl ester 17 reduced both the contractile force and the frequency of guinea pig atria. An antagonism toward the negative influence exerted by endogenous adenosine on the heart seems to be involved in the contractile activity of compound 28. By contrast, compound 17 might be partial agonist at the purinergic inhibitory (A1) receptor. X-ray analysis carried out on 17 and 28 and molecular modeling investigations extended also to related derivatives allowed a possible rationalization between structure and inotropic activity for this series of compounds.

3',5'-Cyclic-AMP Phosphodiesterases↗

Macular pattern dystrophy associated with a mutation of mitochondrial DNA.

PURPOSE/METHODS: To establish association of a macular pattern dystrophy with maternally inherited diabetes and deafness, a new subtype of diabetes mellitus caused by a mutation of mitochondrial DNA (mtDNA). Two probands of two different families with maternally inherited diabetes and deafness were examined. RESULTS/CONCLUSION: Both probands exhibited a macular pattern dystrophy, maternally inherited in one patient. The association of a macular pattern dystrophy with diabetes should lead to screening for a mutation of mtDNA.

Adult↗

A pharmacological, crystallographic, and quantum chemical study of new inotropic agents.

The cardiac activity of a series of milrinone analogues, 2-substituted 3-acyl-1,6-dihydro-6-oxo-5-pyridinecarbonitriles, 1,6,3,2,11,12-hexahydro-6,3-dioxo-5-quinolinecarbonitriles, the correlated carboxylic acids, 2-substituted 3-acyl-6(1H)-pyridones, and 7,8-dihydro-2,5(1H,6H)-quinolinediones, was evaluated in spontaneously beating and in electrically driven atria from reserpine-treated guinea pigs. Their effects were compared with those induced by amrinone and milrinone in both the atria preparations. Compounds SF28 (3-acetyl-1,6-dihydro-2-methyl-6-oxo-5-pyridinecarbonitrile) and SF40 (7,8-dihydro-7-methyl-2,5(1H,6H)-quinolinedione) were the most effective positive inotropic agents. An inhibition of the negative influence exerted by endogenous adenosine on heart preparations seems to be involved in their contractile activity. SF38 (3-benzoyl-2-phenyl-6(1H)-pyridinone), on the contrary, reduced the contractile force and the frequency rate of guinea pig atria with a mechanism not related to an activation of cholinergic or purinergic inhibitory receptors on the heart. X-ray analysis carried out on the three model compounds, SF28, SF40 (positive inotropic agents), and SF38 (negative inotropic agent), and molecular modeling evidenced that the change from phenyl (SF38) to methyl (SF28) or the introduction of a side cyclic aliphatic chain (SF40) results in a variation of conformational preference and topography which may address the different molecules toward distinct receptor pockets according to the resulting inotropic effect.

Amrinone↗

Saponins from Albizzia lucida.

Three main saponins were isolated from the seeds of Albizzia lucida. Their structures were established by spectral analyses and chemical and enzymatic transformations as 3-O-[beta-D-xylopyranosyl(1----2)-alpha-L-arabinopyranosyl (1----6)] [beta-D-glucopyranosyl (1----2)] beta-D-glucopyranosyl echinocystic acid; 3-O-[alpha-L-arabinopyranosyl (1----6)] [beta-D-glucopyranosyl (1----2)]-beta-D-glucopyranosyl echinocystic acid and 3-O-[beta-D-xylopyranosyl (1----2)-beta-D-fucopyranosyl (1----6)-2-acetamido-2-deoxy-beta-D-glucopyranosyl echinocystic acid, characterized as its methyl ester.

Animals↗

Immune responses to herpes simplex virus in patients with recurrent herpes labialis: I. Development of cell-mediated cytotoxic responses.

Groups of subjects during acute (0-3 days) and convalescent (2-3 weeks) phase of recurrent herpes labialis (RHL), and other subjects seropositive or seronegative for herpes simplex virus type 1 (HSV-1) antibody without any history of RHL, were tested for the appearance of cell-mediated cytotoxic responses by stimulating peripheral blood leukocytes (PBL) in vitro with ultraviolet-inactivated HSV-1 antigen, using the release of radiolabelled chromium (51Cr) from HSV-1-infected autologous, or allogeneic lymphocytes and K562 erythroleukemia cell line as nonspecific targets. Development of HSV specific cytotoxic response using autologous targets was essentially limited to subjects with RHL and in HSV antibody seropositive control subjects. Peak activity was observed during the acute phase of the disease, compared to the activity in the convalescent phase in seropositive subjects with RHL, and was preceded by high lymphoproliferative response to HSV. Higher cytotoxic responses against K562 cells were also observed in RHL subjects compared to the controls. Depletion of Leu-2+, Leu-3+ or Leu-11 effector lymphocytes from HSV-1-stimulated PBL cultures by treatment with complement and appropriate monoclonal antibodies resulted in significant reduction of cytotoxicity to HSV-1-infected autologous cells. However, cytotoxicity to K562 cells was reduced only after depletion of Leu-11+ cells. Low levels of allogeneic restriction were observed for cytotoxicity to HSV-1-infected targets. These observations suggest selective activation of virus specific Leu-2+ and Leu-3+ T cell subsets as well as natural killer cell mediated cytotoxic mechanisms during the active phase of recurrences of herpes simplex virus infection.

Adolescent↗

Effects of source leukocyte collection on the immune system.

This study was initiated in order to assess any immunologic effects that source leukocyte concentrate collection might have on double-bag plasmapheresis donors. Previous studies have shown that surveillance parameters, such as T versus non-T lymphocyte subpopulations, showed no abnormal values in donors with as many as 500 visits over a 12-year period. The present study demonstrates that the frequency and the total number of leukocyte donations do not effect the lymphocyte subpopulations and functions observed. No significant changes were noted for specific and nonspecific stimulation, natural killer (NK) cell activity, lymphocyte surface markers and a variety of functional parameters. For example, the apheresis donors manifested no differences in NK cell activity, human leukocyte interferon production, IgG synthesis by B cells and percent suppression of both IgG synthesis and mixed lymphocyte cultures, when compared to non-apheresed donors.

Blood Donors↗

A quantitative determination for the detection of immunoglobulin (IgG) on the surface of platelets.

A sensitive method for the quantitation of IgG on platelets had not been demonstrated until 1975, when Dixon, Rosse, and Ebbert described a quantitative antiglobulin consumption test useful in detecting platelet associated IgG (N Engl J Med 292:230, 1975). A modification of that technique has rendered the assay reproducible and removed the need for daily repetition of a standard IgG titration curve for quantitation. This modification utilizes 1-ethyl-3-3(dimethylaminopropyl)carbodiimide HCl (ECDI) (Sigma, E-7750), in place of chromic chloride, as a coupling agent for attaching IgG (Miles 64-145) to sheep cells (SRC), used as indicator cells. The ECDI consistently couples IgG to SRC and does not subject the SRC to sporadic spontaneous lysis, as does chromic chloride. This modification permits the detection of IgG on platelets (Direct Test), or in sera (Indirect Test) by incubation of a washed platelet pool with sera in vitro, and testing as in the Direct Test. Normal values of 0.01-1.56 and 0.14-1.6 femtograms (F) per platelet have been obtained for the Direct and Indirect Tests, respectively. In six cases of suspected ITP, values ranged 12.0-221.0 F and 2.9-37.6 F for the Direct and Indirect Tests, respectively. In conclusion, in disease states or other abnormal situations, quantities of IgG can be detected that are not usually present on the platelets of normal subjects.

Blood Platelets↗

Increased primary cell-mediated immunity in culture subsequent to adriamycin or daunorubicin treatment of spleen donor mice.

Spleen cell populations from mice treated with Adriamycin or daunorubicin were found to develop a greater complement-independent cellular cytotoxic immune response during culture with allogeneic tumor cells than spleen cells from untreated or cyclophosphamide-treated animals. A temporal and drug dose dependence of this effect was demonstrated. The changes in spleen cell population occurring in the donor mice consequent to drug treatment were evident in the nylon woll-adherent fraction of the spleen cells. The results are consistent with the possibility that the concentration of specific progenitor or accessory cells in the spleen is increased consequent to drug treatment.

Animals↗

Fast- and slow-growing transplantable tumors derived from spontaneous mammary tumors of the DBA/2 Ha-DD mouse.

Nineteen transplantable tumor lines were established from individual spontaneous mammary tumors of the DBA/2 Ha-DD mouse. Of these lines, 5 were classified as fast growing, 8 as medium growing, and 6 as slow growing, based on the time required for the tumors to reach a size of 10 mm in average diameter and on the average survival time of tumor-bearing syngeneic hosts. The relative differences in rate of growth among 5 of these lines remained stable during 11 to 19 transplant generations. In DBA/2J mice, a slow-growing and a fast-growing tumor line were cross-immunogenic. The differences in growth rate between these 2 tumor lines were not primarily related to differences in immunogenicity since they were not abolished in preirradiated hosts. The growth of cell populations from these 2 tumor lines in culture was comparable; however, cells from the fast-growing line had a plating efficiency about 4 times higher than those from the slow-growing line.

Animals↗

The effect of vinblastine on CFU-E in normal and W anaemic mice.

Using a plasma clot technique, we studied the comparative levels of in vitro erythroid colony forming units (CFU-E) of normal and W anaemic mice following intravenous (IV) injection of 6.25 mg/kg of vinblastine (VBL). Mice used in this study were C57Bl/6J, WBB6F1, (+/+,Wv/+ and W/Wv). CFU-E content was looked at on day 0, 1, 3, 5, 7 and 10 following IV VBL. The CFU-E content of bone marrow (BM) and spleen was adequate prior to VBL treatment in all four mouse strains tested. We found IV VBL resulted in a significant rebound of CFU-E production in spleens of all four mouse strains. Most CFU-E production occurred on days 7 and 10 post VBL. The total CFU-E content of BM was not significantly affected by VBL in C57Bl/6J, WBB6F1, +/+ and Wv/+ mice. However, a significant reduction of total CFU-E was seen in the BM of WBB6F1, W/Wv mice. This plus the fact that increased CFU-E is seen in the spleen of all mouse strains including W/Wv suggests that there may be differing cellular or environmental factor(s) in different hematological organs controlling CFU-E of the W/Wv mouse.

Anemia↗

Enhancement of the indirect anti-platelet antibody test and its application to platelet immunology.

Comparisons in the same patients of platelet-bound anti-platelet antibody (APA) levels (direct test) with serum APA levels (indirect test) frequently do not give the same results. Indirect test results frequently are negative or marginally elevated even though platelet-bound antibody is greatly increased on direct testing. The most likely cause for these differences between the two tests is insufficient binding of serum antibody to test platelets in vitro. In an effort to enhance in vitro antibody binding, we examined four test modifications affecting platelet attachment. Rabbit anti-human platelet antisera (absorbed with their specific human donor leukocytes to remove HLA- and granulocyte-specific antibodies) were combined under various conditions with human platelets and tested in a modified antiglobulin consumption test utilizing rabbit IgG. The test conditions varied: incubation time of the serum APA-platelet mixture at 37 degrees C; age of the test platelet pool; ionic strength of the mixture (varied through incorporation of a low-ionic-strength solution (LISS); and vortex agitation for 30 seconds prior to the addition of sera. Optimal attachment in standard phosphate-buffered saline took place in 60 minutes using test platelets stored for either 3 or 30 days, and yielded mean values for rabbit immune sera of 9.9 fg of IgG per platelet. Preincubation controls yielded a mean of 0.7 to 1.5 fg per platelet. Incorporation of LISS or vortexing of test platelets did not affect the results of control, but both modifications substantially increased test values of immune sera to 15.8 and 17.3 fg of IgG per platelet, respectively. Combining LISS with vortexing did not further increase values.

Animals↗