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Biomedical subjects

S Abdou

Publications and source records attributed to S Abdou.

11 recordsLinked to original sources
PubMed2001

Effect of the complexation with cyclodextrins on the in vitro antiviral activity of ganciclovir against human cytomegalovirus.

The toxicity of the molecules currently used in the treatment of human cytomegalovirus (HCMV) in immunocompromised hosts often causes interruption of the therapy. Cyclodextrins (Cds), oligosaccharides possessing a hydrophobic cavity, have the property of forming inclusion complexes with a great number of molecules, improving their bioavailability and their biological properties. In this study, we have tested the ability of three native Cds to improve the antiviral effect of ganciclovir (GCV) on two HCMV strains: AD169, a reference susceptible strain, and RC11, a GCV resistant strain. The efficacy of the GCV, expressed in IC50 values, showed no improvement in the presence of alpha-Cd, while the use of beta- and gamma-Cd improved by 6- and 4-fold, respectively, its antiviral activity tested on AD169 strain. The influence of beta- or gamma-Cd on GCV efficiency evaluated on RC11 strain showed a decrease of the IC50. Parallel NMR studies were undertaken in order to characterize formation of [GCV:Cd] complexes. The results showed that complexation between alpha- or gamma-Cd and GCV did not occur. In contrast, spectra proved that beta-Cd formed an inclusion complex with GCV. This complex was characterized in UV-Visible spectrophotometry and the influence of the beta-Cd on the GCV penetration in cells was measured. The use of Cds as carriers of antiviral drugs would be a good alternative to traditional treatment, because it may allow the administration of lower doses and so continuous treatment by reducing the toxic effects of drugs.

Antiviral Agents↗
PubMed1999

Complexation study and anticellular activity enhancement by doxorubicin-cyclodextrin complexes on a multidrug-resistant adenocarcinoma cell line.

Ability of molecular complexes of [Doxorubicin (DX)-cyclodextrin (Cd)] to enhance the anticellular activity of antineoplastic drug Doxorubicin and to reverse its multidrug resistance has been investigated. A spectroscopic study of the alpha, beta, and gamma-[DX-Cds] complexes has been investigated in relation to their biological effects on a multidrug resistant (MDR) human rectal adenocarcinoma cell line (HRT-18). A ten fold enhancement of DX anticellular activity in presence of beta-cyclodextrin alone was detected.

Antineoplastic Agents↗
PubMed1997

beta-Cyclodextrin derivatives as carriers to enhance the antiviral activity of an antisense oligonucleotide directed toward a coronavirus intergenic consensus sequence.

The ability of cyclodextrins to enhance the antiviral activity of a phosphodiester oligodeoxynucleotide has been investigated. A 18-mer oligodeoxynucleotide complementary to the initiation region of the mRNA coding for the spike protein and containing the intergenic consensus sequence of an enteric coronavirus has been tested for antiviral action against virus growth in human adenocarcinoma cells. The phosphodiester oligodeoxynucleotide only showed a limited effect on virus growth rate (from 12 to 34% viral inhibition in cells treated with 7.5 to 25 microM oligodeoxynucleotide, respectively, at a multiplicity of infection of 0.1 infectious particle per cell). In the same conditions, the phosphorothioate analogue exhibited stronger antiviral activity, the inhibition increased from 56 to 90%. The inhibitory effect of this analogue was antisense and sequence-specific. Northern blot analysis showed that the sequence-dependent mechanism of action appears to be the inhibition of mRNA transcription. We conclude that the coronavirus intergenic consensus sequence is a good target for an antisense oligonucleotide antiviral action. The properties of the phosphodiester oligonucleotide was improved after its complexation with cyclodextrins. The most important increase of the antiviral activity (90% inhibition) was obtained with only 7.5 microM oligonucleotide complexed to a cyclodextrin derivative, 6-deoxy-6-S-beta-D-galactopyranosyl-6-thio-cyclomalto-heptaose+ ++ in a molar ratio of 1:100. These studies suggest that the use of cyclodextrin derivatives as carrier for phosphodiester oligonucleotides delivery may be an effective method for increasing the therapeutic potential of these compounds in viral infections.

Cells, Cultured↗
PubMed1995

Suppression of transplant immunity in experimental trichinellosis.

Skin allograft rejection in Balb/c and C57BL/6J mice following experimental infection with 300 larvae of Trichinella spiralis or Trichinella pseudospiralis was studied. Skin grafts from normal C57BL/6J mice were transplanted to infected Balb/c mice and vice versa at days 3, 10, 20 and 30 post-infection. The clinical criteria for graft rejection, scarring and graft falling, were followed. The results indicated that T. spiralis and T. pseudospiralis infections induced a significant delay in graft rejection when compared to the control groups. A maximum rejection time of 24 days was observed in T. spiralis infected C57BL/6J mice which received skin grafts from Balb/c mice on day 3 post-infection. The rejection in the uninfected control group was on day 7 post transplant. The mean rejection times for transplants on various days post-infection, with both species were very similar. Also, the rejection profiles in Balb/c mice were comparable to that observed in C57BL/6J mice, with a maximum delay of 26 days to rejection again obtained in mice transplanted on day 3 post-infection, for both species. When the skin grafts were performed 5 or 10 days prior to infection, the rejection occurred on day 7, as in the control group. The effect of T. spiralis and T. pseudospiralis soluble larval extracts (TSE or TPE) on graft rejection was also examined. Four intraperitoneal injections of 50 micrograms each of TSE or TPE every 48 h for 7 days did not induce any significant delay in graft rejection. In contrast, secretory antigens prepared from cultured larvae in vitro induced significant delays in graft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Percutaneous mitral valvulotomy in non-optimal candidates.

From 1987 to 1990, 215 patients aged 53 +/- 13 years underwent percutaneous mitral valvulotomy in our institution. Mean gradient dropped on average from 13 +/- 4 to 5 +/- 2 mmHg and mitral valve area increased from 1.0 +/- 0.26 to 1.97 +/- 0.5 cm2 at the end of the procedure. Good results, defined as mitral valve area greater than or equal to 1.5 cm2 and mitral regurgitation less than or equal to 2+ at the end of the procedure, were obtained in 78% of the cases. In 41 patients with a poor anatomical form of mitral stenosis, mean gradient decreased from 12 +/- 3 to 6 +/- 6 mmHg and mitral valve area increased from 1.0 +/- 0.3 to 1.7 +/- 0.5 cm2. Good results were obtained in only 50% of the patients. One third of the 3+ mitral regurgitation occurred in this subgroup of patients. In patients with prior surgical commissurotomy, in elderly people and in patients with associated valvulopathy or prosthetic aortic valve, the success rate was similarly low. A significant inverse relationship was found between X-ray and echo scores on the one hand and mitral valve area at the end of the procedure on the other, thus confirming that the results of percutaneous mitral valvulotomy are related to the anatomical form of mitral stenosis. However, patients with poor anatomical forms can undergo the procedure with an acceptable risk compared to benefit ratio.

Adolescent↗
PubMed1990

Aortic valve area evolution after percutaneous aortic valvuloplasty. A prospective trial using a combined Doppler echocardiographic and haemodynamic method.

The aortic valve area was serially evaluated in 45 patients, mean age 78 years, suffering from severe aortic stenosis who underwent percutaneous aortic valvuloplasty. The aortic valve area was calculated from haemodynamic data prior to and immediately after the procedure using the mean gradient. Serial determinations of the aortic valve area were also obtained 1 day before, 1 day after and 2 months after valvuloplasty from the thermodilution cardiac output and Doppler echocardiography mean left ventricle-to-aorta gradient. The mean gradient significantly decreased from 75 +/- 24 to 42 +/- 16 mmHg (P less than 0.01) when measured from haemodynamic data and from 63 +/- 20 to 41 +/- 13 mmHg (P less than 0.01) when estimated from Doppler-derived data. It rose to 48 +/- 15 mmHg at 2 months (NS). The aortic valve area increased significantly from 0.48 +/- 0.13 to 0.67 +/- 0.29 cm2 (P less than 0.01) when calculated from haemodynamic data, and from 0.53 +/- 0.18 to 0.74 +/- 0.23 cm2 (P less than 0.01) when estimated from Doppler-derived data. It declined to 0.69 +/- 0.27 cm2 at 2 months (NS). Aortic valve area values determined from haemodynamic data and from Doppler-derived data correlated well before valvuloplasty (r = 0.80, P less than 0.01) but poorly afterwards (r = 0.57, P less than 0.01). The aortic valve area was not influenced by valvuloplasty in eight patients. At 2 months, restenosis was apparent in eight patients out of 32 that were re-evaluated. Three patients died within 5 days of the procedure. After an average 12 months' follow-up, eight more patients died. Symptoms were not influenced or recurred in 17 patients, while 17 others remained improved by at least one NYHA functional class. Seven patients were operated on, and there was one operative death. The calculated aortic valve area was significantly greater at the end of the procedure in the patients with persistent improvement compared with those with a poor result (0.83 +/- 0.29 cm2 vs 0.65 +/- 0.14 cm2, P less than 0.05). In conclusion, in this study one third of the patients submitted to percutaneous aortic valvuloplasty had no objective improvement in calculated valve area or early restenosis after 2 months. Functional improvement was observed in one third of the patients. Immediate re-estimation of the aortic valve area from haemodynamic data at the end of the procedure may not reflect the actual effect of valvuloplasty on the aortic orifice.

Aged↗
PubMed1990

Infectivity, reproductive capacity and distribution of Trichinella spiralis and T. pseudospiralis larvae in experimentally infected sheep.

Twelve Merino sheep were experimentally shown to be susceptible to infection with Trichinella spiralis or T. pseudospiralis by feeding on infected carcasses of mice or by oral intubation with recovered muscle larvae. The larvae recovered from the sheep showed variable tissue distribution. The diaphragm and tongue were most affected. The viability of the recovered larvae was confirmed by successful passage in mice. The reproductive capacity of T. spiralis in sheep was higher than that of T. pseudospiralis, and also higher than its reproductive capacity in C57BL/6J mice. The reproductive capacity of T. pseudospiralis in sheep at a lower dose was higher than that observed in mice. However at higher doses, it was significantly lower than that in mice. Therefore, it may be concluded that the sheep may be considered a suitable host for both species of Trichinella.

Animals↗