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Biomedical subjects

D De Vito

Publications and source records attributed to D De Vito.

At least 19 recordsLinked to original sources

Effects of chronic treatment with statins and fenofibrate on rat skeletal muscle: a biochemical, histological and electrophysiological study.

BACKGROUND AND PURPOSE: Skeletal muscle injury by hypolipidemic drugs is not fully understood. An extensive analysis of the effect of chronic treatment with fluvastatin (5 mgkg(-1) and 20 mgkg(-1)), atorvastatin (10 mgkg(-1)) and fenofibrate (60 mgkg(-1)) on rat skeletal muscle was undertaken. EXPERIMENTAL APPROACH: Myoglobinemia as sign of muscle damage was measured by enzymatic assay. Histological and immunohistochemical techniques were used to estimate muscle integrity and the presence of aquaporin-4, a protein controlling water homeostasis. Electrophysiological evaluation of muscle Cl(-) conductance (gCl) and mechanical threshold (MT) for contraction, index of intracellular calcium homeostasis, was performed by the two-intracellular microelectrodes technique. KEY RESULTS: Fluvastatin (20 mgkg(-1)) increased myoglobinemia. The lower dose of fluvastatin did not modify myoglobinemia, but reduced urinary electrolytes, suggesting direct effects on renal function. Atorvastatin also increased myoglobinemia, with slight effects on urinary parameters. No treatment caused any histological damage to muscle or modification in the number of fibres expressing aquaporin-4. Either fluvastatin (at both doses) or atorvastatin reduced sarcolemma gCl and changed MT. Both statins produced slight effects on total cholesterol, suggesting that the observed modifications occur independently of HMGCoA-reductase inhibition. Fenofibrate increased myoglobinemia and decreased muscle gCl, whereas it did not change the MT, suggesting a different mechanism of action from the statins. CONCLUSIONS AND IMPLICATIONS: This study identifies muscle gCl and MT as early targets of drugs action that may contribute to milder symptoms of myotoxicity, such as muscle cramps, while the increase of myoglobinemia is a later phenomenon.

Action Potentials↗

Chlamydia pneumoniae in community-acquired pneumonia: seven years of experience.

OBJECTIVES: To determine the prevalence of Chlamydia pneumoniae in community-acquired pneumonia during a period of seven years. METHODS: Serum samples from 311 patients with pneumonia were evaluated using microimmunofluorescence assay to detect C. pneumoniae -specific IgG and IgM antibodies. RESULTS: Thirty nine patients (12.5%) complied with the diagnostic criteria of acute C. pneumoniae infection (a four-fold rise in the titer of IgG antibody, or a single IgG titer > or = 1:512, or a single IgM titer > or = 1:16). All patients were diagnosed as having pneumonia. Co-infection with other respiratory tract pathogens was found in four patients. CONCLUSIONS: C. pneumoniae is an important cause of pneumonia also in our area. Pneumonia due to this bacterium occurs in the cold months and in early spring; in addition we have observed periods of increased incidence of one years duration and periods of low incidence lasting one-two years. Therapy with macrolides and levofloxacin was effective in all patients with C. pneumoniae infection.

Anti-Bacterial Agents↗

Comparison of two microimmunofluorescence tests for detecting antibodies to Chlamydia pneumoniae.

Two microimmunofluorescence (MIF) tests were compared for detection of antibodies to Chlamydia pneumoniae: the microimmunofluorescence of Washington University and the microimmunofluorescence of Chlamydia Serofia. Concordant positive results at the same dilution were observed for IgG in 37.33% of sera tested and concordant negative results were found in 44%. Variations of one fold dilution were observed in 36 sera. Extensive variations (2-3 two-fold dilutions) in the numeric titer values were observed in 20 serum samples with titers of antibody generally higher in the Chlamydia Serofia MIF than in the Washington MIF, resulting in a diagnosis of current infection in three patients. IgM were found with both methods only in one patient. The discrepancies observed may be due to several factors including the different TWAR strain used as antigen in the two tests and the dilution of the FITC-labelled conjugated anti-human IgG. We think that MIF serology may also be influenced by the type of response of the host that may depend on the "local strain" of C. pneumoniae that may express different antigens or in different amounts in comparison with the strains used by the commercial kit.

Antibodies, Bacterial↗

Gating of myotonic Na channel mutants defines the response to mexiletine and a potent derivative.

BACKGROUND: Myotonia and periodic paralysis caused by sodium channel mutations show variable responses to the anti-myotonic drug mexiletine. OBJECTIVE: To investigate whether variability among sodium channel mutants results from differences in drug binding affinity or in channel gating. METHODS: Whole-cell sodium currents (I(Na)) were recorded in tsA201 cells expressing human wild-type (WT) and mutant skeletal muscle sodium channels (A1156T, hyperkalemic periodic paralysis; R1448C, paramyotonia congenita; G1306E, potassium-aggravated myotonia). RESULTS: At a holding potential (hp) of -120 mV, mexiletine produced a tonic (TB, 0.33 Hz) and a use-dependent (UDB, 10 Hz) block of peak I(Na) with a potency following the order rank R1448C > WT approximately equal A1156T > G1306E. Yet, when assayed from an hp of -180 mV, TB and UDB by mexiletine were similar for the four channels. The different midpoints of channel availability curves found for the four channels track the half-maximum inhibitory value (IC50) measured at -120 mV. Thus differences in the partitioning of channels between the closed and fast-inactivated states underlie the different IC50 measured at a given potential. The mexiletine-derivative, Me7 (alpha-[(2-methylphenoxy)methyl]-benzenemethanamine), behaved similarly but was approximately 5 times more potent than mexiletine. Interestingly, the higher drug concentrations ameliorated the abnormally slower decay rate of myotonic I(Na). CONCLUSIONS: These results explain the basis of the apparent difference in block of mutant sodium channels by mexiletine and Me7, opening the way to a more rationale drug use and to design more potent drugs able to correct specifically the biophysical defect of the mutation in individual myotonic patients.

Cell Line, Transformed↗

Can octahedral t2g6 complexes substitute associatively? The case of the isoelectronic ruthenium(II) and rhodium(III) hexaaquaions.

For the low-spin t2g6 Ru(OH2)6(2+) (delta V++ = -0.4 cm3 mol-1) and Rh(OH2)6(3+) (delta V++ = -4.2 cm3 mol-1) hexaaquaions, the respective Id and Ia water exchange mechanisms had been assigned, mainly on the basis of activation volumes delta V++ and entering ligands effects for water substitution. For Ru(II) the near-zero delta V++ was supposed to be due to the compensation between a positive contribution (the loss of a water molecule) and a negative one (the contraction of the bonds of the five spectator ligands at the transition state). Recently, it has been suggested that Rh(III), because of its higher positive charge, could promote further spectator ligands bond contraction sufficient to change the sign of delta V++ to a negative value. If true, this would be an example of limitation in the use of delta V++ for a direct diagnosis of the mechanism. Quantum chemical calculations including hydration effects show that the activation energies for the water exchange on Rh(OH2)6(3+) via the Ia (114.8 kJ mol-1) and the D pathways is 21.8 kJ mol-1 in favor of the former. In the case of Ru(OH2)6(2+) all attemps to compute a transition state for an interchange mechanism failed, but the calculated delta E++ for the D mechanism (71.9 kJ mol-1) is close to both experimental delta G298++ and delta H298++ values. The calculated delta sigma d(M-O) values of -0.53 A for rhodium(III) and +1.25 A for ruthenium(II) agree with the experimented delta V++ values and suggest Ia and D (or Id) mechanisms, respectively. In the case of Ru(OH2)6(2+) the shortening of the bonds of the five spectator ligands to reach the transition states corresponds to a volume change of -1.7 cm3 mol-1. For Rh(OH2)6(3+) these spectator ligands' volume decrease is much smaller (maximum of -0.8 cm3 mol-1) and the bond lengths of the two exchanging ligands at the transition state are characteristic of an interchange pathway with a small "a" character. Because of the strong RhIII-O bonds, water exchange on Rh(OH2)6(3+) proceeds via the Ia pathway with retention of the configuration, whereas the same reaction of Ru(OH2)6(2+), which has considerably weaker RuII-O bonds, follows the Id or the D mechanism.

Journal Article↗

Pseudomonas aeruginosa antibody detection in cystic fibrosis patients.

Chronic respiratory infection due to Pseudomonas aeruginosa remains the most important prognostic factor in cystic fibrosis patients. One method to lengthen the patient's life is to extend the initial state of the illness with an early diagnosis, before Ps. aeruginosa infection becomes chronic. Often this is difficult because of the young age of the patients. This study tested an immunoenzymatic system to evaluate antibody response against three Ps. aeruginosa purified antigens, alkaline protease, elastase and exotoxin A. We studied 40 patients with cystic fibrosis, 20 affected and 20 unaffected by apparent Ps. aeruginosa infection, also from the bacteriological point of view. Serological and bacteriological results were compared for each patient and showed that serological screening can be useful in young subjects, who often have no bacteriological evidence of Ps. aeruginosa colonization.

ADP Ribose Transferases↗

Antibody response to P. aeruginosa in patients with cystic fibrosis: evaluation of two methods.

The immunological response to Ps. aeruginosa antigens may be a sensitive and early indicator of the colonisation of the lungs with these organisms in patients with cystic fibrosis. This study used an immunoenzymatic system and immunoblotting to evaluate the antibody response of 20 patients without apparent Ps. aeruginosa lung infection. These was an agreement in the results obtained with the two methods in 87.5% of cases.

Antibodies, Bacterial↗

[A case of cutaneous myiasis caused by Dermatobia hominis].

Due to increasing international travelling of European population, tropical parasitic diseases may be imported more frequently in temperate countries. We describe a subject who travelled in Brasil and returned to Italy with a subcutaneous nodule containing a phase-II Dermatobia hominis larva; such larva is reported with photographic documentation.

Animals↗

Antibiotics at sub-inhibitory concentrations and virulence factors of Pseudomonas aeruginosa.

The difficulty of instituting an efficacious therapy against Pseudomonas aeruginosa infections is principally due to the microorganism's antibiotic resistance. The aim of our study was to evaluate the activity of four antibacterial drugs, two penems and two quinolones, on the production of virulence factors. Our results demonstrated that the antibiotics tested have a different behaviour depending on the P. aeruginosa phenotype. Therefore it would be advisable to choose the drug on the basis of the isolated strain phenotype.

Alginates↗

Different serological examinations in cystic fibrosis patients: response to Pseudomonas aeruginosa St-Ag.

Crossed immunoelectrophoresis (CIE), enzyme linked immunosorbent assay (ELISA) and immunoblotting (IMB) were used to look for the presence of anti-bodies to Pseudomonas aeruginosa standard antigen in the sera of cystic fibrosis patients with intermittent (CF +/- P) and chronic (CF + P) colonization. Our results show that CIE is too complex a method to use when monitoring the infection over time, that with ELISA a correlation with the patient's clinical status may be made and that IMB can evidence an early, albeit low, reaction in the CF +/- P patient.

Adult↗

Polarizing response of human polymorphonuclear cells to Vibrio cholerae.

Leucocytes have the capacity to respond to chemotactic factors by becoming morphologically and functionally polarized and this method has been found to be suitable for measurement of chemotaxis. This work evaluates the effect of whole Vibrio cholerae biotype El Tor polarization of human polymorphonuclear (PMN) cells in comparison with strains of V. cholerae NAG, Vibrio alginolyticus and Salmonella typhi. V. cholerae O1 induced, at different cell/bacteria ratios, a significant increase in the percentage of polarized cells compared with PMN cells stimulated with formylmethionyl-leucyl-phenylalanine (FMLP) and the other bacteria tested. The capacity of V. cholerae O1 to induce PMN cell polarization may play a role on the inflammatory response recently described in diarrhoea caused by V. cholerae.

Adult↗

Spontaneous binding of Vibrio cholerae to human leucocytes.

Various lymphocyte subpopulations have the capacity to bind different strains of Gram-negative bacteria. The capacity of a strain of Vibrio cholerae, biotype El Tor, isolated during an outbreak of cholera, to adhere to mononuclear cells isolated from peripheral blood was evaluated. V. cholerae binds to mononuclear cells in a dose-dependent manner. The binding was 76.1% at a cells/bacteria ratio of 1:200 and significantly decreased to 43.1% at a ratio of 1:1. The value of bound bacteria, a marker of the mean number of binding sites on the cell surface, decreased at lower cell/bacteria ratios. Studies on isolated cellular populations demonstrated that 51, 42 and 38%, respectively, of CD4+, CD8+ and B cells were bound by V. cholerae whereas monocytes exhibited a higher binding capacity. The data suggest that the percentage binding of V. cholerae to lymphocytes and monocytes was higher than the percentage found in previous studies with Gram-negative bacteria such as Yersinia enterocolitica, and Salmonella, but similar to Helicobacter pylori. The findings indicate that V. cholerae possesses multiple 'adhesins' such as fimbriae, flagella, haemagglutinins, lipopolysaccharides, and outer membrane proteins. The capacity to bind to blood lymphocytes may reflect the same capacity for the lymphocytes from the gastrointestinal associated lymphoid tissue. This cytoadherence may contribute to the uptake of V. cholerae from the gut and may contribute to activation of B cells and CD4+ lymphocytes.

Adult↗

Determination of antitubercular drugs in human plasma by HPLC through direct injection.

A simple and efficient method is described for the direct determination of Isoniazide (INH) and Pyrazinamide (PZAm) in human plasma, based on reversed-phase HPLC. A number of other antitubercular drugs such as p-Aminosalycylic acid (PAS), Streptomycin (STM) and Ethambutol (ETH) and the major metabolites of the two investigated drugs, namely N-Monoacetylisoniazide (AcINH) and Pyrazinoic acid (PZAc), were shown not to interfere with the assay method. A potential application of the method to routine clinical monitoring of antitubercular drugs is discussed.

Antitubercular Agents↗

[Non-gonococcal urethritis and cervicitis from Chlamydia trachomatis: evaluation by means of chlamydiazine and serology].

Infection from Chlamydia trachomatis (CT) in men with non gonococcal urethritis (NGU) and in women with cervicitis has been investigated by means of Chlamidiazime and serological tests. 32.5% of 120 men with NGU and 8.3% of 12 men with dysuria were positive to Chlamydiazine test. Serological test using anti-CT IgG antibodies gave positive results in 30% of men with NGU and 33.3% of men with dysuria. Positivity to higher-levels (1:64) of anti-CT IgG antibodies were demonstrated in 14.1% of NGU patients and 16.6% of men affected by dysuria. Of 11 women positive to Chlamydiazine test, 8 were affected by cervicitis and 3 had no symptoms. All female partners of Chlamydiazine-positive men with NGU resulted positive to Chlamydiazime test. Serological tests were more frequently positive in asymptomatic partners of men with NGU. These results give further evidence for the aetiological role of CT, and suggest that antigen detection assay is more sensitive in men with NGU and in women with symptomatic cervicitis. On the other hand, serological tests seem more useful in men with dysuria and in asymptomatic women.

Adolescent↗