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Biomedical subjects

P Valenti

Publications and source records attributed to P Valenti.

At least 37 records · Page 2Linked to original sources
PubMed2000

In vitro evaluation of newly developed chalcone analogues in human cancer cells.

PURPOSE: Among flavonoids, chalcones have been identified as interesting compounds having chemopreventive and antitumor properties. We studied a panel of newly developed chalcone analogues (S1-S10) using MDA-MB 231 and MCF-7 ADRr breast cancer cells and the T-leukemic Jurkat cell line. Quercetin was used as the reference compound. METHODS: Antiproliferative activity was evaluated by cell counts performed after 72 h of exposure to the drugs. DNA analysis and redox activity were evaluated using flow cytometry. Apoptosis was assessed by morphological analysis, using YOYO-1 as DNA dye; p-glycoprotein function was ascertained by quantitating the efflux of rhodamine 123. RESULTS: All cells were sensitive to chalcone analogues yielding IC50 in micromolar concentrations with the following order regardless of the multidrug resistance (MDR) status: S1 > S2 > quercetin. S1 and S2, the most active compounds, were selected to evaluate their effect on the cell cycle, apoptosis, redox activity, and modulation of the p-glycoprotein function. No significant perturbation in cell cycle was seen with concentration up to 1 microM after 24 h. After 72 h a slight increase in G2/M block and DNA fragmentation occurred at 10 microM. Morphological analysis of apoptosis showed that chalcone analogues induced apoptosis to a higher extent than quercetin. Redox analysis demonstrated that all substances were able to increase intracellular thiol levels, which returned to baseline value after 24 h for all drugs except quercetin. Production of reactive oxygen species was essentially unaffected by all compounds. Finally, in MDR-positive MCF-7 ADRr cells chalcone analogues were unable to modulate p-glycoprotein function while quercetin was able to. CONCLUSIONS: Newly developed S1 and S2 chalcones have a different but higher antitumor activity than quercetin and could be considered as potential new anticancer drugs.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

A GPS logger and software for analysis of homing in pigeons and small mammals.

A detailed analysis of homing in pigeons and small mammals has remained difficult because the paths of the animals could not be reconstructed precisely. Here, we describe a lightweight global position system (GPS) data logger (35 g including battery and casing; 40 x 68 x 18 mm) that records the flight of pigeons and the path of dogs with an accuracy of +/-12 m. With one battery, the logger runs in continuous mode (1 fix/s) for 3.5 h and in power-saving mode (1 fix/5 s) for about 16 h, and stores a maximum of 100,000 data points that are downloaded to a PC. A module of our public domain software WINTRACK permits a detailed numerical and graphical analysis of path geometry, phases of resting and moving, and path similarity. The device can be adapted to different species provided that satellite signals can be received reliably and that the loggers can be recovered. We expect it to be useful for testing hypotheses about pigeon homing, assessing natural spatial behavior and orientation of many species, and anticipate further miniaturization.

Animals↗
PubMed2000

Synthesis and biological activity of some rigid analogues of flavone-8-acetic acid.

Some rigid analogues of flavone-8-acetic acid are described. Direct in vitro toxicity of the synthesised compounds was evaluated towards four tumoral cell lines and the ability of these compounds to stimulate mouse peritoneal macrophages in culture to become tumoricidal (indirect toxicity) was also studied. All compounds were able to induce direct cytotoxicity only at very high concentrations but showed a remarkable indirect activity. In particular compound 4d was able to significantly increase macrophage lytic properties and has been selected for further investigations.

Animals↗
PubMed2000

Acetylcholinesterase inhibitors for potential use in Alzheimer's disease: molecular modeling, synthesis and kinetic evaluation of 11H-indeno-[1,2-b]-quinolin-10-ylamine derivatives.

Continuing our work on tetracyclic tacrine analogues, we synthesized a series of acetylcholinesterase (AChE) inhibitors of 11H-indeno-[1,2-b]-quinolin-10-ylaminic structure. Selected substituents were placed in synthetically accessible positions of the tetracyclic nucleus, in order to explore the structure-activity relationships (SAR) and the mode of action of this class of anticholinesterases. A molecular modeling investigation of the binding interaction of the lead compound (1a) with the AChE active site was performed, from which it resulted that, despite the rather wide and rigid structure of 1a, there may still be the possibility to introduce some small substituent in some positions of the tetracycle. However, from the examination of the experimental IC50 values, it derived that the indenoquinoline nucleus probably represents the maximum allowable molecular size for rigid compounds binding to AChE. In fact, only a fluorine atom in position 2 maintains the AChE inhibitory potency of the parent compound, and, actually, increases the AChE-selectivity with respect to the butyrylcholinesterase inhibition. By studying the kinetics of AChE inhibition for two representative compounds of the series, it resulted that the lead compound (1a) shows an inhibition of mixed type, binding to both the active and the peripheral sites, while the more sterically hindered analogue 2n seems to interact only at the external binding site of the enzyme. This finding seems particularly important in the context of Alzheimer's disease research in the light of recent observations showing that peripheral AChE inhibitors might decrease the aggregating effects of the enzyme on the beta-amyloid peptide (betaA).

Acetylcholinesterase↗
PubMed2000

Metal complexes of lactoferrin and their effect on the intracellular multiplication of Legionella pneumophila.

The action of bovine lactoferrin saturated with iron, zinc and manganese on the intracellular multiplication of Legionella pneumophila in HeLa cells has been tested. The results obtained showed that lactoferrin did not influence the invasive efficiency of Legionella. The intracellular multiplication of the bacterium was inhibited by apo-lactoferrin and by lactoferrin saturated with manganese and zinc, whereas lactoferrin saturated with iron enhanced the intracellular growth. Experiments in parallel were performed with iron, manganese and zinc citrate to test the effect due to the metal ions alone. Even in this condition the addition of an iron chelate enhanced the multiplication of Legionella while the manganese chelate produced a certain inhibition.

Animals↗
PubMed2000

Modulation of actA gene expression in Listeria monocytogenes by iron.

This study analysed the invasiveness of Listeria monocytogenes into enterocyte-like Caco-2 cells in which iron depletion was achieved by picolinic acid treatment. Both entry and intracellular multiplication varied depending on the endogenous iron content of bacterial and eukaryotic cells. The behaviour within enterocytes was correlated with a 10-fold increased transcription of the actA gene observed in bacterial cells grown under conditions of iron stress.

Bacterial Proteins↗
PubMed2000

Increased expression of periplasmic Cu,Zn superoxide dismutase enhances survival of Escherichia coli invasive strains within nonphagocytic cells.

We have studied the influence of periplasmic Cu,Zn superoxide dismutase on the intracellular survival of Escherichia coli strains able to invade epithelial cells by the expression of the inv gene from Yersinia pseudotuberculosis but unable to multiply intracellularly. Intracellular viability assays, confirmed by electron microscopy observations, showed that invasive strains of E. coli engineered to increase Cu,Zn superoxide dismutase production are much more resistant to intracellular killing than strains containing only the chromosomal sodC copy. However, we have found only a slight difference in survival within HeLa cells between a sodC-null mutant and its isogenic wild-type strain. Such a small difference in survival correlates with the very low expression of this enzyme in the wild-type strain. We have also observed that acid- and oxidative stress-sensitive E. coli HB101(pRI203) is more rapidly killed in epithelial cells than E. coli GC4468(pRI203). The high mortality of E. coli HB101(pRI203), independent of the acidification of the endosome, is abolished by the overexpression of sodC. Our data suggest that oxyradicals are involved in the mechanisms of bacterial killing within epithelial cells and that high-level production of periplasmic Cu,Zn superoxide dismutase provides bacteria with an effective protection against oxidative damage. We propose that Cu,Zn superoxide dismutase could offer an important selective advantage in survival within host cells to bacteria expressing high levels of this enzyme.

Base Sequence↗
PubMed2000

Two-stage flexor tendon grafting in children.

Two-stage flexor tendon grafting is a procedure to salvage severely injured flexor tendon systems. It is a complex procedure that requires a surgeon's experience and the cooperation of the child, parents, and a therapist. The results are best in older children (10 to 15 years old) when using the Paneva Holevitch's technique with a suture in the palm of the hand. A continuing problem is always the future of the graft and the growth potential in children.

Adolescent↗
PubMed1999

Bovine lactoferrin peptidic fragments involved in inhibition of herpes simplex virus type 1 infection.

Bovine lactoferrin (BLf) prevents the infection of some enveloped and naked viruses. To identify BLf sequences responsible for the antiviral activity, we tested 31 HPLC fractions, derived from tryptic digestion of BLf, toward herpes simplex virus type 1 (HSV-1). Only a few HPLC purified fragments were active against HSV-1, even if at lower extent than the native undigested BLf. Two large fragments, one corresponding to the C-lobe (amino acid sequence 345-689) and the other corresponding to a large portion of the N-lobe (1-280), were inhibitors of HSV-1 infection, while a smaller part of the N-lobe (86-258) was ineffective. Among the low-molecular-weight fragments, only two small peptides, which coeluted in a single chromatographic peak, were effective towards HSV-1. These peptides, both present in the N-lobe, were identified as peptides 222-230 (ADRDQYELL) and 264-269 (EDLIWK). The same peptides, chemically synthesised, were able to inhibit HSV-1 infection only when they were assayed in association.

Animals↗
PubMed1999

Apoptosis of Caco-2 intestinal cells invaded by Listeria monocytogenes: protective effect of lactoferrin.

The apoptosis of infected hepatocytes is a critical step in nonspecific defense against Listeria monocytogenes infection. We have observed that infection by L. monocytogenes in enterocyte-like cells (Caco-2) results in apoptosis. However, a large fraction of infected intestinal epithelial cells escape from cellular condensation and fragmentation, typical of programmed cell death, and become necrotic. The balance between apoptosis and necrosis seems to be influenced by the number of internalized bacteria. The presence of 1 mg/ml of bovine lactoferrin, an iron-binding protein, added to monolayers before the bacterial infection, decreases the number of internalized bacteria and therefore the overall number of dead cells, and, more importantly, all dead cells are killed by apoptosis and not necrosis.

Animals↗
PubMed1999

Flavone and xanthone derivatives related to fluoroquinolones.

A number of flavone and xanthone derivatives bearing some characteristic features of fluoroquinolones such as the fluorine atom and an ortho piperazine ring are described. The new compounds have been tested for possible cytotoxic and antimicrobial activities. Cytotoxicity of both groups of compounds is rather poor, while the antibacterial activity is restricted to xanthones.

Anti-Infective Agents↗
PubMed1999

A novel gene encoding a sulfur-regulated outer membrane protein in Thiobacillus ferrooxidans.

Thiobacillus ferrooxidans is a Gram-negative chemolithotrophic bacterium able to oxidize ferrous iron, elemental sulfur and inorganic sulfur compounds. The oxidation of sulfur by T. ferrooxidans resulted in an expression of some outer membrane proteins (OMPs) at a level higher than that observed during ferrous iron oxidation. Among these OMPs, a protein with a molecular mass of 54 kDa was purified and 18 amino acids of the N-terminal sequence determined. Using a 54 bp PCR generated DNA product as a probe for the protein, we isolated a 4.5 kb Pst I DNA chromosomal fragment containing the corresponding gene. Sequencing 2169 bp of this fragment revealed the open reading frame codifying for the protein, consisting of 467 amino acids and a molecular mass of 49,674 Da. The mature protein was produced by the removal of a 32 amino acid signal peptide-like sequence from the N-terminus of a 499 amino acid peptide. Although no significant homology with any known protein has been found and its physiological role remains unclear, its high expression on sulfur substrates suggests a role in sulfide mineral oxidation.

Amino Acid Sequence↗
PubMed1999

Inhibition of poliovirus type 1 infection by iron-, manganese- and zinc-saturated lactoferrin.

In this study we investigated the inhibitory activity of different milk proteins on poliovirus infection in Vero cells. Proteins analyzed were mucin, alpha-lactalbumin, beta-lactoglobulin, and bovine and human lactoferrin. Viral cytopathic effect was not prevented by mucin, alpha-lactalbumin or beta-lactoglobulin, whereas the lactoferrins tested were able to inhibit the replication of poliovirus in a dose-dependent manner. Further experiments were carried out in which apo- and native lactoferrin or lactoferrin fully saturated with ferric, manganese or zinc ions were added to the cells during different phases of viral infection. Results obtained demonstrated that all lactoferrins were able to prevent viral replication when present during the entire cycle of poliovirus infection or during the viral adsorption step. Only zinc lactoferrin strongly inhibited viral infection when incubated with the cells after the viral attachment, being the inhibition directly correlated with the degree of zinc saturation. Our results demonstrated that all lactoferrins interfered with an early phase of poliovirus infection; zinc lactoferrin was the sole compound capable of inhibiting a phase of infection subsequent to virus internalization into the host cells.

Animals↗
PubMed1999

Left-hemispheric superiority for visuospatial orientation in homing pigeons.

To test for lateralisation of visuospatial orientation during homing, pigeons who had binocularly learned the homeward route from remote release sites were tested monocularly on either their left or their right eye for homing performance. In two experiments with three different release sites, birds using their right eye showed considerably better homing performance. If sun compass information was available, there was no difference in the direction of vanishing. Without this information, a difference between pigeons using their left or right eye emerged. Results show that visuospatial orientation in birds can be lateralised in favour of the left brain hemisphere and lend further support to the view that vision is important for pigeons homing on a familiar route. Cognitive mechanisms which might account for the observed pattern of lateralisation are discussed.

Animals↗
PubMed1999

Arterial anatomy and clinical application of the dorsoulnar flap of the thumb.

After injection of stained latex at the brachial artery, the arterial supply of the dorsal aspect of the thumb was studied by light microscopy in 25 cadavers. An artery, located on the dorsoulnar side and connecting the head of the first metacarpal with the dorsal arcade of the proximal nail fold, was found in all dissections. We report the results of the anatomic study and the clinical applications of a dorsoulnar skin flap that can be raised on its artery with a distal pedicle. Clinical experience is based on 32 flaps. In 25 cases this flap was used for distal skin loss coverage (palmar or dorsal) of the thumb as an island flap. In 7 cases it was used for reconstruction of the finger pulp (5 index and 2 middle fingers) in the form of a cross-finger flap.

Cadaver↗
PubMed1999

[Humanitarian surgery of the hand. Our experience in Vietnam].

After a general presentation of the geographical and social aspects of Vietnam, the authors describe the conditions of their surgical work during short time humanitarian hand surgery missions. These missions, lasting 7 to 10 days are dedicated to the care of children, and a half-day of teaching for Vietnamese corresponding surgeons. The technical and material limits, the constraints for the patients to travel to the hospital, to pay for care and the difficulties of follow-up, require the selection of patients in whom the disease can be treated in a single stage procedure. Three types of diseases were treated: congenital anomalies, post-burn and post-trauma sequelae. Typical cases of these diseases are described and shown. Due to the absence of hand rehabilitation, reconstructive tendon surgery is inadvisable to avoid disappointing poor results and discredit this part of hand surgery. For reason of complexity and unreliability of electromyographic examination, brachial plexus injuries cannot be treated, except the simplest cases needing one or two tendon transfers. Concerning skin coverage and reconstructive surgery, our experience has shown that pedicled local and locoregional flaps, and even microsurgical transfers are adapted and reliable techniques due to the imperative of single stage procedure. The education and teaching of young surgeons in European teams and regular relation-ships with corresponding surgeons from developing countries are certainly the best way to promote humanitarian hand surgery.

Altruism↗
PubMed1999

[Neurocutaneous flap of the anteromedial aspect of the thigh with a distal pedicle. Anatomical study and clinical application].

The authors report an anatomic study of the vascularization of the medial aspect of the thigh on 21 cadaveric dissections with injection. They describe a neuro-cutaneous medial thigh flap, with a distal pedicle, vascularised by proximal branches of the saphenous artery (branch from the descending genicular artery). This flap includes the medial femoral cutaneous nerve, which runs with a supra-aponeurotic vascular network. The anatomic variants and harvesting technique of this flap are described. Our clinical experience is based on 3 patients operated between 1996 and 1998, for coverage of an amputation stump. The results were excellent in all cases with a follow-up of 6 months to 3 years. The good quality of this skin coverage allows satisfactory adaptation of the leg prosthesis in our cases.

Adult↗