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A J Molina

Publications and source records attributed to A J Molina.

5 recordsLinked to original sources

Comparative study of hyaluronic derivatives: rheological behaviour, mechanical and chemical degradation.

Depolymerisation by oxytetracycline (OTC) as well as the progressive cleavage of hyaluronic acid induced by ultrasound was investigated in nine commercially available hyaluronic polymers. Sample solutions differed in molecular weight, from 500 to 7000 kDa, and in their source. The hyaluronic acid concentration in each sample was analysed by HPLC. The concentration range was over 8.39-10.18 mg ml(-1) in samples with a nominal concentration of 1%, and 14.05 mg ml(-1) in one sample with a nominal concentration of 1.5%. It was found that stability was dependent on both molecular weight and the concentration of the samples. The rheological parameters n (power law index) and K (consistency coefficient) were good predictors regarding the degradation behaviour. Although many factors are involved in obtaining a therapeutic response, the results obtained in this work support the notion that both mechanical and chemical degradation are reduced in hyaluronate solutions with low molecular weight, the final concentration of the product being a critical factor.

Biocompatible Materials↗

Improved LC method to determine ivermectin in plasma.

A simple, rapid and sensitive high-performance liquid chromatographic (HPLC) method has been developed to quantify Ivermectin (IVM) in plasma using an isocratic system with fluorescence detection. The method included a fast liquid phase extraction using cold methanol. HPLC separation was carried out by reversed phase chromatography with a mobile phase composed of methanol:acetonitrile:water with 0.2% acetic acid (45:50:5 v/v/v), pumped at flow rate of 2 ml min(-1). Fluorescence detection was performed at 365 nm (excitation) and 475 nm (emission). The calibration curve for IVM was linear from 0.25 to 100 ng ml(-1). The validation method yielded good results regarding linearity, precision, accuracy, specificity and recoveries. The values of the limit of detection (LOD) and limit of quantification (LOQ) were 0.032 and 0.167 ng ml(-1), respectively.

Chromatography, High Pressure Liquid↗

Effect of clotrimazole on microsomal metabolism and pharmacokinetics of albendazole.

Albendazole is a broad spectrum anthelmintic drug widely used in human and veterinary medicine. Intestinal and hepatic albendazole metabolism leads to albendazole sulfoxide (active metabolite) and albendazole sulfone (inactive metabolite) formation. Microsomal sulfonase activity can be abolished by in-vitro interaction with clotrimazole and pharmacokinetic studies confirm this interaction. After albendazole incubation, albendazole sulfone formation was completely inhibited by 50 microM clotrimazole in intestinal incubations and a 50% inhibition was observed in hepatic incubations. The lower inhibition constant (K(i)) value observed in the intestinal incubations (9.4 +/- 1.0 microM) compared with the hepatic counterparts (23.3 +/- 15.8 microM) pointed to a greater affinity of the enzymatic systems in the intestine. Regarding the formation of albendazole sulfoxide, an inhibition close to 50% was observed in liver and intestine at 10 microM clotrimazole. The pharmacokinetic parameters obtained following the oral co-administration of albendazole sulfoxide and clotrimazole corroborated the in-vitro inhibition of albendazole sulfone formation, since the ratio of the area under the plasma concentration-time curves for the sulfoxide/sulfone (AUC(ABZSO)/AUC(ABZSO2)) was significantly higher (38.1%). In addition, the AUC and C(max) for albendazole sulfone were significantly lower. The effect of clotrimazole was also studied after prolonged treatment. Hepatic microsomal metabolism of albendazole was induced after 10 days of clotrimazole administration, with significant increases in formation of albendazole sulfoxide (40%) and sulfone (27%). These results offer further insight into the metabolism of benzimidazole drugs and highlight the difficulty involved in human therapy with these anthelmintics, since after prolonged treatment the drug interactions are affected differentially.

Administration, Oral↗

Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects.

Toxicities have limited the use of allogeneic hematopoietic cell transplantation (HCT) to younger, medically fit patients. In a canine HCT model, a combination of postgrafting mycophenolate mofetil (MMF) and cyclosporine (CSP) allowed stable allogeneic engraftment after minimally toxic conditioning with low-dose (200 cGy) total-body irradiation (TBI). These findings, together with the known antitumor effects of donor leukocyte infusions (DLIs), led to the design of this trial. Forty-five patients (median age 56 years) with hematologic malignancies, HLA-identical sibling donors, and relative contraindications to conventional HCT were treated. Immunosuppression involved TBI of 200 cGy before and CSP/MMF after HCT. DLIs were given after HCT for persistent malignancy, mixed chimerism, or both. Regimen toxicities and myelosuppression were mild, allowing 53% of eligible patients to have entirely outpatient transplantations. Nonfatal graft rejection occurred in 20% of patients. Grades II to III acute graft-versus-host disease (GVHD) occurred in 47% of patients with sustained engraftment. With median follow-up of 417 days, survival was 66.7%, nonrelapse mortality 6.7%, and relapse mortality 26.7%. Fifty-three percent of patients with sustained engraftment were in complete remission, including 8 with molecular remissions. This novel allografting approach, based on the use of postgrafting immunosuppression to control graft rejection and GVHD, has dramatically reduced the acute toxicities of allografting. HCT with the induction of potent graft-versus-tumor effects can be performed in previously ineligible patients, largely in an outpatient setting. Future protocol modifications should reduce rejection and GVHD, thereby facilitating studies of allogeneic immunotherapy for a variety of malignancies. (Blood. 2001;97:3390-3400)

Adult↗