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Biomedical subjects

A Giacometti

Publications and source records attributed to A Giacometti.

At least 19 recordsLinked to original sources

Pseudospectral approach to inverse problems in interface dynamics.

An improved scheme for computing coupling parameters of the Kardar-Parisi-Zhang equation from a collection of successive interface profiles is presented. The approach hinges on a spectral representation of this equation. An appropriate discretization based on a Fourier representation is discussed as a by-product of the above scheme. Our method is first tested on profiles generated by a one-dimensional Kardar-Parisi-Zhang equation, where it is shown to reproduce the input parameters very accurately. When applied to microscopic models of growth, it provides the values of the coupling parameters associated with the corresponding continuum equations. This technique compares favorably with previous methods based on real space schemes.

Journal Article↗

Prophylaxis against Staphylococcus aureus vascular graft infection with mupirocin-soaked, collagen-sealed dacron.

A rat model was used to investigate the efficacy of mupirocin in the prevention of vascular prosthetic graft infections. The effect of mupirocin-soaked Dacron was compared with the effect of rifampin-soaked, collagen-sealed Dacron in the rat model of graft infection caused by methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus. Graft infections were established in the back subcutaneous tissue of 195 adult male Wistar rats by implantation of 1-cm(2) Dacron prostheses followed by topical inoculation with 5 x 10(7) colony-forming units of S. aureus. The study included a control group (no graft contamination), two contaminated groups that did not receive any antibiotic prophylaxis, two contaminated groups in which perioperative intraperitoneal amoxicillin clavulanate prophylaxis (50 mg/kg) was administered, four contaminated groups that received mupirocin- or rifampin-soaked graft, and four contaminated groups that received mupirocin- or rifampin-soaked graft and perioperative intraperitoneal amoxicillin clavulanate prophylaxis (50 mg/kg). The grafts were sterilely removed 7 days after implantation and the infection was evaluated by using sonication and quantitative agar culture. Data analysis showed that the efficacy of mupirocin against both strains was significantly different from that of the untreated control. In addition, mupirocin was more effective than rifampin against the methicillin-resistant strain. Finally, only the combination of mupirocin and amoxicillin clavulanate produced complete suppression of growth of all strains.

Amoxicillin-Potassium Clavulanate Combination↗

Therapeutic efficacy of the polymyxin-like peptide ranalexin in an experimental model of endotoxemia.

BACKGROUND: A rat model was used to investigate the efficacy of a polycationic peptide, the polymyxin-like ranalexin, in the prevention of lethality in a rat model of septic shock. The effect of ranalexin was compared with those of polymyxin B and imipenem. METHODS: Adult male Wistar rats (weight range: 250-300 g) were used for all the experiments. The study included five groups: an uninfected control group C(0), an untreated control group C(1), and three drug-treated groups that received 1 mg/kg ranalexin (group 2), 20 mg/kg imipenem (group 3), and 3 mg/kg polymyxin B (group 4). Rats, with the exception of the uninfected control group (C(0)), were given an intraperitoneal injection of 2 x 10(10) colony-forming units of Escherichia coli. Each group included 15 animals. Bacterial growth in abdominal exudate and plasma; endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma, and mortality were evaluated. RESULTS: Results were evaluated 48 h after inoculation. Ranalexin, imipenem, and polymyxin B significantly reduced the lethality (survival was 93.3, 80.0, and 93.3%, respectively) and the growth of E. coli both in abdominal fluid and plasma compared with saline treatment. Ranalexin showed higher antimicrobial activity than polymyxin B and imipenem and, at the same time, exhibited an antiendotoxin activity similar to that of polymyxin B (< or =0.015 EU/mL). Finally, ranalexin and polymyxin B significantly reduced plasma TNF-alpha levels (< or =4 pg/mL). CONCLUSION: Monodose ranalexin treatment prevents bacterial growth, endotoxemia, and mortality in rats with septic shock.

Animals↗

Aerosolization of an anionic surfactant (LAS) and dissolved organic carbon (DOC) under laboratory conditions.

Aerosolization of natural salt and brackish waters under laboratory conditions is responsible for the transfer of synthetic surfactants such as linear alkylbenzene sulphonate (LAS) from water to the atmosphere. Excluded the lagoon sample which stands apart, on the average ca. 45% of the LAS present at concentrations between 0.1 and 4.1 microg l(-1) in the tested coastal and offshore marine and lagoon waters was transferred to the aerosol extract. The distribution of the individual LAS homologs in the aerosol is very similar to that in water, which indicates no preferential removal from the bulk water of any LAS homolog. The fraction of dissolved organic carbon (DOC) undergoing aerosolization under the same conditions for each tested sample was on an average ca. 3.3%, corresponding to ca. 5.6 mg l(-1). On the average, the enrichment factor of the sea samples, resulting from the changing of the LAS/DOC ratio before and after aerosolization, was ca. 20.

Aerosols↗

Electrophoretic karyotyping and antifungal susceptibility patterns of Candida parapsilosis clinical isolates causing deep and superficial fungal infections.

Forty-six isolates of Candida parapsilosis, each from a single patient, were collected from July 1993 through March 1999 at the University of Ancona Hospitals and Clinics. Twenty-eight strains were isolated from superficial lesioned sites, including skin, nails and other sources while 18 strains were isolated from blood. The isolates were typed by electrophoretic karyotyping (EK) and tested for their susceptibility to fluconazole (FLC), itraconazole (ITC), flucytosine (5-FC), and amphotericin B (AMB). Our data confirmed that EK is a useful technique for DNA typing of isolates of Candida parapsilosis and showed that the source of isolation is not associated with a given DNA type. Although strains belonging to this species of Candida are susceptible to the most common antifungals, including the triazoles, the degree of ITC susceptibility was dose dependent (MIC ranging from 0.25-0.5 microgram/ml) for 98% of the isolates.

Antifungal Agents↗

Structure-function relationship of three triple-helical nucleic acids.

The nucleic acid triplexes poly d(T) x poly d(A) x poly d(T), poly (U) x poly (A) x poly (U), and poly (I) x poly (A) x poly (I) display a sort of continuity between each other. However, their morphologies present their own individuality which, considering those of their parent duplexes, are quite unexpected. This comparison helps to understand triplex structure-function relationship. While helical parameters are functions of the sugar pucker, low values of WC and Hoogsteen base-pair propellers is commonplace for triplexes and the Hoogsteen base-pair geometry monitors the effects of the interstrand phosphates charge-charge repulsion.

Nucleic Acid Conformation↗

Activity of buforin II alone and in combination with azithromycin and minocycline against Cryptosporidium parvum in cell culture.

The in vitro anti-cryptosporidial activity of buforin II alone and in combination with azithromycin and minocycline was investigated. Buforin II showed moderate activity, which increased with increasing concentration to 55.7% suppression of growth at 20 microM. Moreover, its activity was enhanced when it was combined with either azithromycin or minocycline with >90% parasite reduction at the highest concentration tested. Buforin II may be active in inhibiting Cryptosporidium parvum growth in vitro upon combination with either azithromycin or minocycline.

Animals↗

Effect of mono-dose intraperitoneal cecropins in experimental septic shock.

OBJECTIVE: To investigate the efficacy of three cecropins, cecropin A, cecropin B, and cecropin P1, in preventing lethality in a rat model of septic shock. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory in a university hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Rats were given an intraperitoneal injection of 2 x 10(10) colony forming units of Escherichia coli, with the exception of the uninfected control group (C0). Animals were randomized to receive, immediately after bacterial challenge, intraperitoneally isotonic sodium chloride solution (untreated control group C1), 1 mg/kg cecropin A (group 2), 1 mg/kg cecropin B (group 3), 1 mg/kg cecropin P1 (group 4), 20 mg/kg imipenem (group 5), or 60 mg/kg piperacillin (group 6). Each group included 15 animals. MEASUREMENTS AND MAIN RESULTS: We measured bacterial growth (quantitative agar culture) in abdominal exudate and plasma, endotoxin and tumor necrosis factor-alpha concentration in plasma, and mortality. Results were evaluated at 48 hrs after inoculation. Cecropins, piperacillin, and imipenem significantly reduced the lethality and the number of E. coli in abdominal fluid compared with saline treatment. In addition, cecropin B significantly decreased the lethality compared with piperacillin treatment. Finally, only cecropins significantly reduced plasma endotoxin concentration. CONCLUSIONS: Mono-dose cecropin treatment prevents bacterial growth, endotoxemia, and mortality in rats with septic shock. Cecropin B was the most effective compound in reducing all variables measured.

Animals↗

Interactions of posaconazole and flucytosine against Cryptococcus neoformans.

A checkerboard methodology, based on standardized methods proposed by the National Committee for Clinical Laboratory Standards for broth microdilution antifungal susceptibility testing, was applied to study the in vitro interactions of flucytosine (FC) and posaconazole (SCH 56592) (FC-SCH) against 15 isolates of Cryptococcus neoformans. Synergy, defined as a fractional inhibitory concentration (FIC) index of <0.50, was observed for 33% of the isolates tested. When synergy was not achieved, there was still a decrease in the MIC of one or both drugs when they were used in combination. Antagonism, defined as a FIC of >4.0, was not observed. The in vitro efficacy of combined therapy was confirmed by quantitative determination of the CFU of C. neoformans 486, an isolate against which the FC-SCH association yielded a synergistic interaction. To investigate the potential beneficial effects of this combination therapy in vivo, we established two experimental murine models of cryptococcosis by intracranial or intravenous injection of cells of C. neoformans 486. At 1 day postinfection, the mice were randomized into different treatment groups. One group each received each drug alone, and one group received the drugs in combination. While combination therapy was not found to be significantly more effective than each single drug in terms of survival, tissue burden experiments confirmed the potentiation of antifungal activity with the combination. Our study demonstrates that SCH and FC combined are significantly more active than either drug alone against C. neoformans in vitro as well in vivo. These findings suggest that this therapeutic approach could be useful in the treatment of cryptococcal infections.

Animals↗

Combination studies between polycationic peptides and clinically used antibiotics against Gram-positive and Gram-negative bacteria.

The in vitro interaction between five polycationic peptides, buforin II, cecropin P1, indolicidin, magainin II, and ranalexin, and several clinically used antimicrobial agents was evaluated against several clinical isolates of Gram-positive and Gram-negative aerobic bacteria, using the microbroth dilution method. The combination studies showed synergy between ranalexin and polymyxin E, doxycycline and clarithromycin. In addition, magainin II was shown to be synergic with betalactam antibiotics.

Amino Acid Sequence↗

In-vitro activity and killing effect of polycationic peptides on methicillin-resistant Staphylococcus aureus and interactions with clinically used antibiotics.

The in-vitro activity of nisin, a 34-residue peptide produced by several Lactococcus lactis strains, and ranalexin, a 20-residue peptide isolated from the skin of the bullfrog Rana catesbeiana, alone and in combination with amoxycillin, amoxycillin-clavulanate, imipenem, clarithromycin, ciprofloxacin, rifampin and vancomycin was investigated against 40 nosocomial isolates of methicillin-resistant Staphylococcus aureus (MRSA). All isolates were inhibited at concentrations of 1 to 32 microg/ml. Synergy was observed when the peptides were combined with other agents, with the exception of the beta-lactams. Finally, the consecutive exposures to each peptide did not result in selection of stable mutants with decreased susceptibility. Our finding show that nisin and ranalexin are active against MRSA, and that their activity is enhanced when they are combined with several antimicrobial agents.

Amoxicillin↗

Environmental and serological evidence for the presence of toxocariasis in the urban area of Ancona, Italy.

To evaluate the Toxocara spp. eggs environmental contamination of the soil of the urban or suburban area Ancona (Italy), 22 public playgrounds were selected and several cores of soil were taken from any selected areas. To study the Toxocara seroprevalence in the inhabitants of Ancona, blood samples were collected from selected groups of individuals. One hundred and sixty-three blood samples were tested using an enzyme linked immunosorbent assay (ELISA) technique (Lofarma Lab, Milan, Italy) for the detection of IgG-specific antibodies to T. canis excretory-secretory antigens. Toxocara spp. eggs were found in the soil samples from 14 (63.6%) playgrounds. Toxocara seroprevalence was detected in blood specimens from six (8.1%) out of 74 symptomatic individuals and from one (1.1%) out of 89 asymptomatic controls. Among symptomatic individuals, the association between Toxocara seroprevalence and eosinophilia resulted statistically significant (p = 0.029). The high environmental contamination frequency found make necessary to prompt preventive public health measures, such as control of stray animals, treatment of infected pets and hygiene education of the population.

Adolescent↗

Efficacy of rifampin-levofloxacin as a prophylactic agent in preventing Staphylococcus epidermidis graft infection.

OBJECTIVES: To investigate the efficacy of levofloxacin in the prevention of vascular prosthetic graft infection in a rat model. METHODS: Graft infections were established in the subcutaneous tissue of 225 male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with methicillin-susceptible and methicillin-resistant S. epidermidis. The study included a group without contamination, two contaminated groups without prophylaxis, two contaminated groups with intraperitoneal levofloxacin prophylaxis, two contaminated groups with intraperitoneal cefazolin prophylaxis, two contaminated groups with intraperitoneal teicoplanin prophylaxis and six contaminated groups with rifampin-soaked graft and intraperitoneal levofloxacin, cefazolin or teicoplanin prophylaxis. The grafts were removed after 7 days and evaluated by quantitative culture. RESULTS: The efficacy of levofloxacin against the methicillin-susceptible strain was not different to that of cefazolin or teicoplanin. Levofloxacin showed slight less efficacy than teicoplanin against the methicillin-resistant strain. The combination levofloxacin-rifampin demonstrated to be similarly effective to the combination rifampin-teicoplanin and more effective than the combination rifampin-cefazolin against both strains. CONCLUSIONS: Rifampin-levofloxacin combination seems useful for the prevention of late-appearing vascular graft infections caused by S. epidermidis.

Animals↗

Structure of poly (dT).poly (dA).poly (dT).

The molecular structure of poly (dT).poly (dA).poly (dT) has been determined and refined using the continuous x-ray intensity data on layer lines in the diffraction pattern obtained from an oriented fiber of the DNA. The final R-value for the preferred structure is 0.29 significantly lower than that for plausible alternatives. The molecule forms a 12-fold right-handed triple-helix of pitch 38.4 A and each base triplet is stabilized by a set of four Crick-Watson-Hoogsteen hydrogen bonds. The deoxyribose rings in all the three strands have C2'-endo conformations. The grooveless cylindrical shape of the triple-helix is consistent with the lack of lateral organization in the fiber.

DNA↗

Structure of Poly (U).poly (A).poly (U).

The molecular structure of poly (U).poly (A).poly (U) has been determined and refined using the continuous x-ray intensity data on layer lines in the diffraction pattern obtained from an oriented fiber of the RNA. The final R-value for the preferred structure is 0.24, far lower than that for the plausible alternatives. The polymer forms an 11-fold right-handed triple-helix of pitch 33.5A and each base triplet is stabilized by Crick-Watson-Hoogsteen hydrogen bonds. The ribose rings in the three strands have C3'-endo, C2'-endo and C2'-endo conformations, respectively. The helix derives additional stability through systematic interchain hydrogen bonds involving ribose hydroxyls and uracil bases. The relatively grooveless cylindrical shape of the triple-helix is consistent with the lack of lateral organization.

DNA↗

Structure of poly (I).poly (A).poly (I).

The molecular structure of poly (I).poly (A).poly (I) has been determined and refined using the continuous intensity data on layer lines in the x-ray diffraction pattern obtained from an oriented fiber of this polymorphic RNA complex. The polymer forms a 12-fold right-handed triple-helix of pitch 39.7A and each base-triplet is stabilized by quasi Crick-Watson-Hoogsteen hydrogen bonds. The ribose rings in all the three strands have C3'-endo conformations. The final R-value for this best structure is 0.24 and the x-ray fit is significantly superior to all the alternative structures where the different chains might have different furanose conformations. This all-purine triple-helix, counter-intuitively, has a diameter roughly 3A shorter than that of DNA and RNA triple-helices containing a homopurine and two complementary homopyrimidine strands. Its compact, grooveless cylindrical shape is consistent with the lack of lateral organization.

Adenine↗

Anticryptosporidial activity of ranalexin, lasalocid and azithromycin alone and in combination in cell lines.

The in vitro anticryptosporidial activities of ranalexin, lasalocid and azithromycin alone and in combination were investigated against four clinical isolates of Cryptosporidium parvum. Susceptibility was tested by inoculating the isolates on to cell monolayers and determining the parasite count after 48 h incubation at 37 degrees C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of the above-mentioned compounds. Ranalexin showed moderate anticryptosporidial activity: at a concentration of 64 mg/L it reduced parasite counts by 33.8%. Azithromycin at a concentration of 8 mg/L gave inhibition comparable to that observed with the highest concentration of ranalexin. Lasalocid showed the highest activity, with a 70.3% reduction in parasite counts at 2 mg/L. The combination of ranalexin 64 mg/L and lasalocid 2 mg/L completely suppressed parasite growth without harming the monolayer.

Acquired Immunodeficiency Syndrome↗

Activity of nitazoxanide alone and in combination with azithromycin and rifabutin against Cryptosporidium parvum in cell culture.

The in vitro activity of nitazoxanide alone and in combination with azithromycin and rifabutin was investigated against four clinical isolates of Cryptosporidium parvum. The susceptibility tests were performed by inoculation of the isolates on toe cell monolayers and determination of the parasite count after 48 h incubation at 37 degrees C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of each agent. Antibiotic-free plates were used as controls. Experiments were performed in triplicate. Nitazoxanide showed moderate anticryptosporidial activity: it suppressed the growth of parasites by >50% at 8 mg/L. A parasite reduction of 79.8-83.9% was observed when nitazoxanide 8 mg/L was combined with azithromycin 8 mg/L and rifabutin 8 mg/L. The study suggests that nitazoxanide may be active in inhibiting C. parvum growth in vitro upon combination with azithromycin or rifabutin.

AIDS-Related Opportunistic Infections↗