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Biomedical subjects

J Alberola

Publications and source records attributed to J Alberola.

28 records · Page 2Linked to original sources

Pharmacokinetics of meglumine antimoniate after administration of a multiple dose in dogs experimentally infected with Leishmania infantum.

Pharmacokinetics of meglumine antimoniate in dogs with experimentally induced leishmaniosis has been investigated. After infection, dogs received a dose of 75 mg kg-1 of meglumine antimoniate twice daily by subcutaneous injection for 10 days. Blood samples were collected throughout the treatment. No statistical differences were found in the kinetic behaviour of the drug administered as a single dose to healthy dogs and that administered as a multiple dose to infected animals. However, peak plasma concentrations (Cmax) of 30.8 +/- 12.8 micrograms ml-1 found after this dosage regimen were higher than those observed after the single dose administration of 100 mg kg-1 24 h-1. Furthermore, sustained antimony concentrations of 1.14 +/- 0.52 micrograms Sb ml-1 were detected throughout the treatment. No signs of toxicity were found in the animals treated indicating that this regimen would be very appropriate to treat canine leishmaniosis.

Analysis of Variance↗

Antibody response to human cytomegalovirus (HCMV) glycoprotein B (gB) in AIDS patients with HCMV end-organ disease.

Human cytomegalovirus (HCMV)-specific antibody responses in HIV-1 infected individuals either with or without HCMV end-organ disease were examined to determine the whether development of HCMV disease was associated with a particular deficit in the antibody response. Antiwhole HCMV, anti-glycoprotein B (gB), and neutralizing antibody levels were higher in HIV-1 infected individuals than in healthy immunocompetent subjects, particularly in patients with AIDS either with or without HCMV-associated disease. Irrespective of location and spread of HCMV disease, patients who had received anti-HCMV therapy prior to sampling exhibited significantly higher anti-gB and neutralizing antibody titers than those who remained untreated. Likewise, patients with HCMV disease who were antigenemic or viremic had significantly lower anti-gB and neutralizing antibody titers than those who tested negative in either assay. Patients with untreated HCMV disease had significantly lower antibody titers than AIDS patients without disease. Analysis of the IgG subclass antibody responses to gB revealed no significant differences among HIV-1 infected individuals. These results suggest that levels of detectable anti-gB and HCMV neutralizing antibodies are inversely related to systemic viral load. Thus, antibodies with such specificities may be relevant in preventing the establishment of HCMV-associated disease or in modulating its progression.

AIDS-Related Opportunistic Infections↗

Pharmacokinetics of liposome-encapsulated meglumine antimonate after intramuscular and subcutaneous administration in dogs.

Controlling canine leishmaniasis may reduce the incidence of human leishmaniasis, which affect immunocompromised persons, especially those with human immunodeficiency virus infection. Thus, the pharmacokinetics of liposome-encapsulated meglumine antimonate (LMA) in dogs was studied after intramuscular (I.M.) and subcutaneous (S.C.) administration. Serum concentration-time data for both forms of administration were best described by a triexponential open model. The absorption phase showed statistically significant differences between I.M. and S.C. administrations (K01(I.M.) = 0.046/min, K01(S.C.) = 0.025/min). The first phase of decrease of plasma concentrations showed a longer half-life for S.C. than for I.M. administration, with the delay being caused by the slow absorption process after S.C. injection. Mean terminal phase half-lives after administration of I.M. and S.C. were 904.1 min and 637.4 min, respectively. Peak plasma concentrations after administration of I.M. (Cmax = 43.8 microg/ml) and S.C. (Cmax = 24.9 microg/ml) were detected at 42.8 min and 79.8 min, respectively. Urinary excretion of antimony for both routes surpassed 80% during the first 6 hr, with the rest of the drug being excreted slowly over the following 18 hr. The results obtained with this formulation suggest that for treating canine leishmaniasis, it would be more advisable to inject LMA intramuscularly if we assume that the significantly higher Cmax observed after I.M. administration is more relevant to dog's clinical outcome than is maintenance of concentrations over longer periods.

Animals↗

Disposition of antimony after the administration of N-methylglucamine antimoniate to dogs.

A study was carried out in dogs to define the pharmacokinetic profile of antimony and to define a better therapeutic protocol for the treatment of canine leishmaniasis. Six healthy beagle dogs received 100 mg/kg of N-methylglucamine antimoniate containing 27.2 per cent of antimony intravenously, intramuscularly and subcutaneously. After intravenous administration the plasma concentration of antimony decreased rapidly and after 240 minutes it was lower than the ED50 values suggested for Leishmania donovani. The pharmacokinetic parameters and bioavailability of antimony were calculated after each route of administration in each dog. The curves of plasma concentrations vs time were best described by a triexponential open model with a mean (sd) half life t1/2 alpha of 9.4 (4.4) min, a t1/2 beta of 45.3 (4.5) min and a t1/2 gamma of 618.0 (93.5) min. The mean volume of distribution at steady state was 0.25 (0.03) litres/kg and the total body clearance was 0.25 (0.04) litres/h/kg. The peak plasma concentration (Cmax) after intramuscular administration was 27.2 (3.1) micrograms/ml, and after subcutaneous administration it was 25.5 (4.5) micrograms/ml; they were reached after 73.6 (11.9) min and 85.6 (11.3) min, respectively. The bioavailabilities after intramuscular and subcutaneous administration were 91.7 (7.1) and 92.2 (7.1) per cent, respectively. More than 80 per cent of the antimony was excreted in the urine in the first nine hours.

Animals↗

Effect of age on theophylline pharmacokinetics in dogs.

Differences between neonatal and adult animals in their response to drugs can usually be attributed to altered disposition processes. Effect of age on the pharmacokinetics of theophylline was determined after IV administration of the drug to 10 groups of dogs at 1, 2, 3, 4, 8, 12, 16, 24, 52, and 104 weeks of age. Plasma theophylline concentration curves for all groups were adjusted to a biexponential kinetic, with rapid initial distribution phase and slower elimination phase. It also was noticed that young dogs have a slower elimination half-life (1 week old, t 1/2 beta = 987 minutes) than do older animals (8 weeks old, t 1/2 beta = 138 minutes). The values then plateaued until 16 weeks of age, increasing slightly at more advanced age (104 weeks old, t 1/2 beta = 282 minutes). A similar pattern was followed with respect to clearance (1-week-old pups, Cl = 1.17 ml/min/kg of body weight), which increased progressively to reach a value of 7.09 ml/min/kg at 16 weeks of age, then decreased to 3.5 ml/min/kg at 104 weeks of age. Volume of distribution beta, in relation to body weight, was not significantly different between age groups (between 1.2 and 1.6 L/kg; P < or = 0.03). Theophylline biotransformation mechanisms may be mainly responsible for Cl and t 1/2 beta variations. This leads us to suggest that quantitative and qualitative modifications in the P-450 mono-oxygenase system are responsible for the variations observed in pharmacokinetic variables of theophylline between dogs of different ages. These findings may have clinical relevance with regard to therapeutic range of theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Adh expression in species of the mulleri subgroup of Drosophila.

The locus encoding the NAD-dependent alcohol dehydrogenase (alcohol:NAD oxidoreductase; EC 1.1.1.1) is duplicated in some species of the cactophilic mulleri subgroup of Drosophila. Here we report a survey on the expression throughout development and in different tissues for this system, its regulation using interspecific hybrids, and the effects induced by 2-propanol in 10 species belonging to four different clusters of the above-mentioned subgroup. Our results indicate different expression throughout development and in different tissues, cis regulation in hybrid ovaries, trans (-) regulation in hybrid adults, and different responses to 2-propanol.

1-Propanol↗

Study of haemostatic disorders in experimentally induced leishmaniasis in Beagle dogs.

Haemostatic alterations in dogs experimentally infected with Leishmania infantum were studied before and after therapy with meglumine antimonate. Haemostatic function tests including platelet count, collagen-induced platelet aggregation, prothrombin time, activated partial thromboplastin time, thrombin time, plasma fibrinogen determination, and serum fibrinogen/fibrin degradation products concentration were performed. In the course of infection and before treatment, moderate thrombocytopenia (P<0.00001), decreased collagen induced platelet aggregation (P=0.0003), prolonged thrombin time (P=0.0117) and increased fibrinogen/fibrin degradation products were observed. Statistically significant differences of plasma fibrinogen concentration, prothrombin time, and activated partial thromboplastin time were not encountered. Haemostatic parameters returned to normal values after therapy. The results indicate that Leishmania infection may impair haemostasis suggesting induction of disseminated intravascular coagulation (DIC), and that treating dogs in an early stage of infection may potentially avoid the possibility of developing an uncompensated DIC.

Animals↗

Thrombocytopathia and light-chain proteinuria in a dog naturally infected with Ehrlichia canis.

A 6-year-old dog was presented for evaluation of recurrent epistaxis. Platelet counts, biochemical tests, and coagulation tests were within the normal range, but a mucosal bleeding time was prolonged; there was hyperproteinemia and a monoclonal gammopathy. Heterogeneity of light chains appeared in urine, however, thus suggesting that the gammopathy was polyclonal. Platelet aggregation tests showed decreased responsiveness to collagen. An Ehrlichia canis indirect fluorescent-antibody titer was positive (1:40). Treatment with tetracycline, melphalan, and prednisone resulted in a rapid clinical improvement that persisted for at least 3 years.

Animals↗

[Echography, a diagnostic method in testicular abscess].

We report on 10 patients who presented with a scrotal mass. The diagnosis of testicular abscess was made on ultrasonographic examination of the scrotal mass. The sensitivity and specificity rates of the foregoing imaging technique were 100%. Furthermore, it permitted determining with precision the extent and degree of involvement of the following structures: testes, epididymis, spermatic cord and scrotal layers.

Abscess↗