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Biomedical subjects

P Vidal

Publications and source records attributed to P Vidal.

At least 19 recordsLinked to original sources

[Quality of life in HIV-infected children and adolescents under highly active antiretroviral therapy: change over time, effects of age and familial context].

OBJECTIVE: To evaluate Quality of life (QoL) of HIV-infected children under highly active antiretroviral therapies, and its change over 18 months. MATERIALS AND METHODS: QoL was evaluated by self-administred questionnaires (french versions of AUQUEI, OK-ado, and compilation of both) in 23 young living with HIV/AIDS (6-15 yrs), under antiretroviral multitherapies, and re-evaluated 18 months later in 19 of them. RESULTS: At baseline, QoL in HIV-infected children-adolescents was relatively good. The answers given to each items and the mean score from infected children were similar to those obtained in uninfected healthy children. Moreover, infected adolescents distinguished definitly from healthy adolescents, describing higher QoL. The mean satisfaction score from the whole group decreased between M0 and M18 (mainly in the youngests), and mainly concerned 3 fields (self-esteem, health and school) while their somatic health remained stable or improved. An effect of the familial context was also observed for these 3 fields. CONCLUSION: The progressive decline of QoL in HIV-infected children, and the surprising high and steady level of satisfaction over-time provided by the adolescents, underlined the frailty of this population and the need for a psychologic management associated to the medical follow-up. Such a multidisciplinary approach should take into account the preoccupations and difficulties of each age-class, those linked to the diagnosis itself, and to the familial or scolar contexts, in order to preserve QoL of this pediatric population, as far as possible, in a long term.

Adolescent↗

Analgesic-antiinflammatory properties of Proustia pyrifolia.

The antiinflammatory (per os and topic) and analgesic (per os) properties of the aerial part of Proustia pyrifolia a species in danger of extinction were investigated, and the major compounds of two of its active extracts were isolated. In addition, the evaluation of cytotoxicity in three tumoral cell lines and the acute toxicity of the crude methanol extract were also assayed, together with the antioxidant activity for the different extracts of this species. The results of the evaluation of the topic antiinflammatory activities induced by arachidonic acid, and phorbol 12-myristate 13-acetate of the different extracts showed that this species possesses active constituents that could diminish cyclo-oxygenase and lipoxygenases activities, the enzymes that allow the synthesis of proinflammatory endogenous substances as prostaglandin E(2) and leukotrienes, respectively. Our results corroborate the antiinflammatory and analgesic effects of Proustia pyrifolia, and could justify its use in folk medicine for the treatment of rheumatic and gout illnesses. From bio-active extracts beta-sitosterol, quercetin and dihydroquercetin were obtained, and these compounds could explain in part the antiinflammatory, analgesic and antioxidant activities of this species. The crude methanol extract did not present acute toxicity or cytotoxic activity, however only this extract exhibited antioxidant activity.

Analgesics↗

Major degradation product identified in several pharmaceutical formulations against the common cold.

Different pharmaceutical preparations against the common cold containing acetaminophen, phenylephrine hydrochloride, and chlorpheniramine have been studied. An unidentified degradation product has been discovered in these preparations after short- and long-term stability studies, with increasing concentration at increasing storage temperatures and times. LC/MS was employed to identify and obtain molecular weights of the degradation products using an electrospray ionization interface. To obtain detailed structural information on the major degradation product, its isolation by SPE followed by HPLC was required. Final isolation was accomplished by using a new pentafluorophenyl stationary phase. Once the major degradation product was isolated, MS/MS, 1H NMR, 13C NMR, COSY, HMBC, and HSQC techniques permitted the complete characterization of this new compound formed under the usual stability conditions at climatic chambers. Its origin was also established as a result of the interaction between two of the components in the formulation. It is important to remark that this compound has not been described in the literature up to now and that, moreover, it has been identified in several commercial preparations containing phenylephrine hydrochloride and chlorpheniramine maleate.

Chromatography, High Pressure Liquid↗

Multicenter study on spreading of the tet(M) gene in tetracycline-resistant Streptococcus group G and C isolates in Argentina.

A prospective multicenter study on invasive infections caused by beta-hemolytic streptococci was performed over 6 months and involved 42 centers from 16 cities in Argentina. Among 33 isolates recovered, 9 group G Streptococcus isolates (39.1%) and 2 group C Streptococcus isolates (20%) exhibited resistance to tetracycline and harbored the tet(M) gene. Genealogical analysis revealed that tetracycline resistance has a polyclonal origin in Argentina.

Argentina↗

Doxorubicin-peptide conjugates overcome multidrug resistance.

A well-known mechanism leading to the emergence of multidrug-resistant tumor cells is the overexpression of P-glycoprotein (P-gp), which is capable of lowering intracellular drug concentrations. To overcome this problem, we tested the capability of two peptide vectors that are able to cross cellular membranes to deliver doxorubicin in P-gp-expressing cells. The antitumor effect of peptide-conjugated doxorubicin was tested in human erythroleukemic (K562/ ADR) resistant cells. The conjugate showed potent dose-dependent inhibition of cell growth against K562/ADR cells as compared with doxorubicin alone. Doxorubicin exhibited IC50 concentrations of 65 microM in the resistant cells, whereas vectorized doxorubicin was more effective with IC50 concentrations of 3 microM. After treatment of the resistant cells with verapamil, the intracellular levels of doxorubicin were markedly increased and consequent cytotoxicity was improved. In contrast, treatment of resistant cells with verapamil did not cause any further enhancement in the cell uptake nor in the cytotoxic effect of the conjugated doxorubicin, indicating that the conjugate bypasses the P-gp. Finally, we show by the in situ brain perfusion method in P-gp-deficient and competent mice that vectorized doxorubicin bypasses the P-gp present at the luminal site of the blood-brain barrier. These results indicate that vectorization of doxorubicin with peptide vectors is effective in overcoming multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Infection of ascending aortic graft: treatment with surgical cleaning, graft preservation and transposition of muscle flaps. Report of two cases].

Mediastinitis with graft infection is a serious complication of ascending aorta replacement. We report two cases of graft infection, treated with surgical cleaning, graft preservation and transposition of muscle flaps. A 62 years old male was admitted 34 days after an ascending aortic grafting due to a sternal dehiscence and mediastinitis. Antimicrobial treatment was started and a surgical cleaning performed, leaving an open sternotomy. Three days later, the thoracic cavity was closed with a rectus abdominis muscle flap. After 23 months of follow up, the patient is well and without evidence of infection. A 74 years old male was subjected to an aortic valve and ascending aorta replacement and a myocardial revascularization. In the postoperative period, the patient developed septic signs, and a purulent drainage. A CAT scan showed a liquid collection surrounding the aortic graft. On tW Sixteenth postoperative day, a surgical cleaning was performed and the thorax was closed with the pectoralis major muscle. After 10 months of follow up, the patient is in Good condition and without evidence of infection.

Aged↗

Ebola and Marburg virus antibody prevalence in selected populations of the Central African Republic.

With the natural history of the filovirus family seemingly unknown, filovirus ecology in its natural environment remains a rudimentary field of research. In order to investigate the maintenance cycle of filovirus in Central Africa, a study was conducted within the rain forest of the Central African Republic. The epidemiological study determines the frequency and distribution of filovirus seroprevalence in a selected human population. Using an ELISA, serum samples from Pygmy and non-Pygmy populations were tested for Ebola-Zaire virus and Marburg (MBG) virus antibody. Filovirus antibody reacting sera were found in all zones investigated, and in all populations studied (Ebola virus IgG 5.3%; Marburg virus IgG 2.4%). Pygmies appeared to have a significantly higher seroprevalence (P < 0.03) against Ebola-Zaire virus (7.02%) than non-Pygmies (4.2%). MBG virus or related unknown filovirus strains also seem to be present in the western part of Central Africa. MBG virus antibodies were present in different Pygmy groups (ranging from 0.7 to 5.6%, mean 2.05%) and in several non-Pygmy populations (ranging from 0.0 to 3.9%, mean 3.4%) without an overall significant difference between the two groups (P = 0.14). The potentialities of nonpathogenic filovirus strains circulating in the Central African Republic are discussed.

Antibodies, Viral↗

A paleoepidemiologic study of diffuse idiopathic skeletal hyperostosis.

OBJECTIVE: To investigate the prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in ancient populations. MATERIAL AND METHODS: We studied 38 women and 61 men aged at least 30 years at death, whose remains were recovered from four cemeteries of the High Middle Ages (VIth to VIIIth century) located in Lorraine (eastern France). Criteria previously developed by Crubézy and Crubézy-Ibanez for paleopathological studies were used to determine whether the skeletal remains exhibited definite, possible, probable, or no DISH. RESULTS: Definite DISH with flowing ossification along the thoracic spine and ossification of peripheral enthesopathies was seen in 2.8 to 3.7% of the subjects from two cemeteries and in none from the other two cemeteries. Identical figures were found for possible DISH. The prevalence and male predominance s (nine of 13 subjects in any DISH category were males) were similar to those reported in contemporary studies and in other paleopathological studies. CONCLUSION: In the absence of clinical data on the metabolic status of the study subjects, our results suggest that DISH in our subjects was a marker for older age at death.

Adult↗

[Streptococcus pyogenes: penicillin and erythromycin susceptibility in the cities of Neuquen and Cipolletti].

Penicillin resistance has not yet been detected in Streptococcus pyogenes. However macrolide-resistant streptococci have emerged in several countries. Only low rates of erythromycin-resistant S. pyogenes were reported in Argentina, with the exception of a 11.1% observed in Mendoza. The aim of the present study was to determine the susceptibility to penicillin and to erythromycin of 251 consecutive clinically-significant isolates of S. pyogenes obtained from four centers of Cipolletti and Neuquén during the period April-December 1998. The double disk test with erythromycin and clindamycin disks was employed as a screening method to detect ERY-resistant streptococci and to determine the phenotype of macrolide resistance. Disk diffusion was also employed for determining penicillin susceptibility. Macrolide-resistant isolates were also tested for penicillin, ceftriaxone, erythromycin, clindamycin and azithromycin susceptibility by the agar dilution method. Additionally they were also tested for erythromycin susceptibility by E-test (AB Biodisk, Solna, Sweden). All streptococci studied were susceptible to penicillin and thirty of them (12.0%) were resistant to erythromycin. All these resistant isolates were also resistant to azithromycin but susceptible to ceftriaxone and clindamycin. They showed the phenotype M (probably efflux-mediated mechanism) and the MICs of erythromycin ranged between 8 and 16 micrograms/ml. According to these results we conclude that in spite of universal susceptibility to penicillin in S. pyogenes, macrolide resistance is a matter of concern in Neuquén and Cipolletti. At least in those cities it appears to be necessary to routinely perform macrolide susceptibility tests in beta-hemolytic streptococci.

Anti-Bacterial Agents↗

Antiphospholipid antibodies and retinal thrombosis in patients without risk factors: a prospective case-control study.

PURPOSE: To determine the prevalence of antiphospholipid antibodies and other immunologic abnormalities in patients with occlusive retinal vascular events, exempt from conventional risk factors of retinal thrombosis. METHODS: Forty patients with retinal vascular occlusion (26 with retinal vein occlusions, eight with arterial occlusions, two with combined venous and arterial occlusions, and four with venous occlusions plus vasculitis), free of main accepted risk factors for retinal thrombosis, were prospectively screened for antiphospholipid antibodies (anticardiolipin-antibodies and lupus anticoagulant) and other immunologic abnormalities. Fourteen patients were younger than 50 years. Prevalence and mean values of antiphospholipid antibodies (aPL) were compared with those in a homogeneous control group of 40 patients. RESULTS: The prevalence of antiphospholipid antibodies in the study group was 22.5% (nine of 40). Comparison with control group prevalence (5% [two of 40]) showed a statistically significant difference (P = .04). Six patients in the study group disclosed positivity for IgG-anticardiolipin antibodies, one patient for IgM anticardiolipin antibodies, and two patients for both isotypes IgG and IgM anticardiolipin antibodies. The antibody assay for lupus anticoagulant was negative for all patients. Three patients were diagnosed as having primary antiphospholipid antibody syndrome and are undergoing systemic anticoagulant therapy. Relevant immunologic abnormalities were also found (27.5% with antinuclear antibodies, 35% with elevation of circulating immune complexes, 35% with complement deficiency, 30% with positive rheumatoid factor, and 17.5% with positive C-reactive protein). Thirteen patients (32.5%) had more than four parameters altered. No significant association was found between prevalence or mean values of anticardiolipin antibody and patients younger than 50 years. CONCLUSIONS: The high prevalence of anticardiolipin antibodies in patients with vaso-occlusive retinopathy exempt from conventional risk factors, and the relevant diagnostic and therapeutic implications, lead us to recommend a systematic search for specific antiphospholipid antibodies in such patients.

Adult↗

Studies on keratinophilic fungi. XI. Chrysosporium undulatum sp. nov.

Chrysosporium undulatum sp. nov., showing intermediate characteristics between Chrysosporium and Malbranchea, is described and illustrated. This taxon is characterised by long and curved to loosely coiled hyphal appendages, deflected to wavy fertile hyphae forming dense tufts and small, subglobose, frequently intercalary, verrucose conidia. Restriction enzyme analysis and comparison of sequences of the ITS1-5.8S-ITS2 ribosomal DNA region of the most similar species strongly support this proposal.

Animals↗

Interactions of primary amphipathic vector peptides with membranes. Conformational consequences and influence on cellular localization.

The conformations of two peptides produced by the combinations of a nuclear localization sequence and a sequence issued from the fusion protein gp41 of HIV 1 have been analyzed both in solution and in membranes or in membrane mimicking environments. Both are shown to be nonordered in water, alpha-helical when incorporated into SDS micelles where the helical domain concerns the hydrophobic part of the peptides. Interactions with lipids induce the formation of beta-sheet and the lipid-peptide interactions are governed by the nature of the lipid polar headgroups. A monolayer study shows that replacement of the sequence separating the two sequences with an arginine favors the lipid-peptide interactions which may contribute to the understanding of the different, nuclear and membrane associated, cellular localizations of the peptides.

Amino Acid Sequence↗

Design of carrier peptide-oligonucleotide conjugates with rapid membrane translocation and nuclear localization properties.

Peptides containing a hydrophobic motif associated with a nuclear localization signal separated by various linkers were synthesized in solid phase. The hydrophobic sequence corresponds either to a signal peptide sequence or to a fragment of the fusion peptide of GP41 while the hydrophilic sequence is that of a nuclear localization signal. The C-termini of these peptides bear a cysteamide group that was linked to a fluorescent probe. This allowed the cellular localization of the probe to be determined as a function of the peptide sequences. The labeled peptides were then incubated with fibroblasts. Using N-biotinylated derivatives we confirmed by indirect immunofluorescence that the observed localizations corresponds to those of the peptides. The presence of a linker appears to play a role in the cellular localization. One of these peptides was successfully used to target fluorescent oligodeoxynucleotides into living cells demonstrating improved cell delivery of peptide-oligodeoxynucleotide conjugates.

Amino Acid Sequence↗

Immunohistochemical localization of nephrocalcin, a kidney-specific glycoprotein, to renal cell carcinoma.

OBJECTIVES: Nephrocalcin (NC), an acidic glycoprotein produced by renal proximal tubule cells and functioning as an inhibitor of calcium oxalate monohydrate crystalization, has been previously shown to have increased urinary excretion in patients with renal cell carcinoma (RCC). The current study uses immunohistochemical techniques to localize NC to cells of primary RCC. METHODS: We studied 29 kidneys removed because of RCC. Slides were deparaffinized and stained after incubating with anti-NC antibody by using the avidin-biotin-peroxidase complex techniques. Uptake of stain by tumor cells and adjacent normal renal cells was compared. RESULTS: Twenty-seven kidneys (93%) showed positive staining for RCC tumor cells; 2 kidneys staining positive for normal proximal tubule cells failed to stain adjacent RCC tumor cells (7%). CONCLUSIONS: The data suggest that enhanced production of urinary NC in patients with RCC derives from cells of the primary tumor.

Adolescent↗

Transvaginal sonography in endometrial carcinoma: preoperative assessment of the depth of myometrial invasion in 50 cases.

OBJECTIVE: A prospective study was designed for patients previously diagnosed of endometrial carcinoma to evaluate the accuracy of transvaginal sonography (TVS) in determining both the presence and the depth of myometrial invasion. Patients with advanced stage disease (III and IV) were specifically excluded from the analysis. SUBJECTS AND METHODS: Sixty patients with endometrial carcinoma underwent transvaginal ultrasonography. Ten of these patients were ruled out due to various reasons. In the remaining 50 cases, TVS findings were compared with those obtained after total abdominal hysterectomy and bilateral salpingo-oophorectomy (AHT). RESULTS: The sensitivity of TVS in detecting deep invasion, i.e. more than 50% of the myometrial thickness was 94.1%, while the specificity was 84.8% and the overall accuracy was 88%. Following the classification of the International Federation of Obstetrics and Gynecology, stage I, which divides myometrial invasion into three categories (none, superficial involvement and deep invasion) sensitivity was 66.2%, specificity was 83.1% and overall accuracy was 77.2%. CONCLUSION: These findings are consistent with those reported in literature with regard to overall accuracy of TVS. Results are similar to those obtained with magnetic resonance imaging (MRI) without contrast and slightly lower than MRI plus contrast.

Endometrial Neoplasms↗

A preliminary study of the occurrence of actidione-resistant fungi in sediments of Catalonian river mouths (Spain). I. Keratinolytic fungi and related Onygenales.

Sediments from eight river mouths along the Catalonian coast (Spain) were surveyed for keratinolytic fungi and related Onygenales. The actidione plating technique was employed. Of 532 actidione-treated sediment samples, 268 (50.3%) were positive for the fungi. Altogether, 384 fungal strains from 35 species were isolated from the samples. Narasimhella marginospora, Aphanoascus fulvescens, Neoarachnotheca keratinophila with its anamorph Myriodontium keratinophilum, Narasimhella hyalinospora, Beauveria alba, Sporothrix schenckii, Chrysosporium lobatum and Gymnoascus littoralis were the predominant species in sediments. Abundance of N. marginospora was clearly correlated with the degree of water pollution with sewage.

Journal Article↗

Effects on mollicutes (wall-less bacteria) of synthetic peptides comprising a signal peptide or a membrane fusion peptide, and a nuclear localization sequence (NLS) -- a comparison with melittin.

In order to investigate the effect of primary amphipathic peptides on mollicutes (wall-less bacteria), we have synthesised five molecules (P1, P2, P3, JM123, and JM133) comprising a 16 to 18-residue hydrophobic sequence and the nuclear localization sequence (NLS) PKKKRKV of simian virus 40 large-T antigen, C-terminated by a cysteamide group. The hydrophobic cluster was in P1 the signal sequence of the heavy chain of Caiman crocodilus immunoglobulin G and in JM123 the fusion peptide of human immunodeficiency virus 1 glycoprotein gp41 in which phenylalanine7 was replaced by a tryptophan residue. The homologues P2, P3, and JM133 were obtained by slight alterations of these sequences. Circular dichroism spectroscopy revealed that, in liposomes, P-series peptides were mainly under the form of beta-sheets whereas JM-series peptides displayed a high proportion of turns. These peptides proved to be bactericidal for some mollicutes, notably Acholeplasma laidlawii, but were much less potent than melittin. Furthermore, their antibiotic activity was independent of the average thickness of the plasma membrane hydrophobic core whilst that of melittin was inversely related to the thickness. Melittin and the synthetic peptides abolished spiroplasma cell motility and helicity, but only melittin and P-series peptides split the cells into globular forms displaying an average diameter of ca. 1 microm. In contrast to melittin, the synthetic peptides agglutinated spiroplasmas, suggesting that their polycationic NLS was exposed on the cell surface. P-series peptides decreased, though less efficiently than melittin, A. laidlawii and Spiroplasma melliferum membrane potential (delta psi) and transmembrane pH gradient (delta pH), at concentrations much lower than their minimal inhibitory concentrations whilst JM-series peptides had no effect on delta psi and delta pH in the same conditions. Actually, the bactericidal activity of these peptides towards mollicutes was proportional to their ability to collapse the electrochemical transmembrane potential.

Alligators and Crocodiles↗

Conformations of primary amphipathic carrier peptides in membrane mimicking environments.

Two peptides designed for drug delivery were generated by the combination of a signal peptide with a nuclear localization sequence and are shown to facilitate the cellular internalization of small molecules which are covalently linked to these peptides. In order to understand the mechanism of internalization, the conformations of the peptides were investigated through different approaches both in solution and in membrane-mimicking environments. These peptides are highly versatile and adopt different conformational states depending on their environment. While in a disordered form in water, they adopt an alpha-helical structure in TFE and in the presence of micelles of SDS or DPC. The structured domain encompasses the hydrophobic part of the peptides, whereas the charged C-termini remain unstructured. In contrast, in the presence of lipids and whatever the nature of the phosphate headgroup, the two peptides mainly adopt an antiparallel beta-sheet form and embed in the lipidic cores. This result suggests that the beta-sheet is responsible for the translocation through the cellular membranes but also questions the conformational state of signal peptides when associated to hydrophilic sequences.

Amino Acid Sequence↗