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Biomedical subjects

Alicia R Gascón

Publications and source records attributed to Alicia R Gascón.

14 recordsLinked to original sources
PubMed2006

Chemistry and the biological response against immunoisolating alginate-polycation capsules of different composition.

Implantation of microencapsulated cells has been proposed as a therapy for a wide variety of diseases. An absolute requirement is that the applied microcapsules have an optimal biocompatibility. The alginate-poly-L-lysine system is the most commonly applied system but is still suffering from tissue responses provoked by the capsule materials. In the present study, we investigate the biocompatibility of microcapsules elaborated with two commonly applied alginates, i.e. an intermediate-G alginate and a high-G alginate. These alginates were coated with poly-L-lysine (PLL), poly-D-lysine (PDL) and poly-L-ornithine (PLO). The main objective of this study is to determine the interaction of each alginate matrix with the different polycations and the potential impact of these interactions in the modulation of the host's immune response. To address these issues the different types of microcapsules were implanted into the peritoneal cavity of rats for I month. After this period the microcapsules were recovered and they were evaluated by different techniques. Monochromatised X-ray photoelectron spectroscopy (XPS) was performance and the degree of capsular recovery, overgrowth on each capsule, and the cellular composition of the overgrowth were evaluated by histology. Our results illustrate that the different observed immune responses are the consequence of the variations in the interactions between the polycations and alginates rather than to the alginates themselves. Our results suggest that PLL is the best option available and that we should avoid using PLO and PDL in its present form since it is our goals to produce capsules that lack overgrowth and do not induce an immunological response as such.

Alginates↗
PubMed2005

Preparation of sustained release hydrophilic matrices by melt granulation in a high-shear mixer.

PURPOSE: The objective of this work was to prepare theophylline sustained release matrix tablets based on the combination of hydroxypropyl methylcellulose (HPMC K4M and K100M) and different meltable binders by melt granulation in a high-shear mixer. METHODS: Dissolution profiles of each formulation were compared to those of TheoDur 200 mg tablets and the mean dissolution time (MDT) and similarity factor (f2 factor) were calculated. The matrices swelling behavior was investigated by texture analysis. RESULTS: The results obtained show that the type of excipient influenced the drug release rate. In particular, the dissolution rate was delayed when lipophilic binders were used and only formulations containing Gelucire 50/13 or PEG 6000 with HPMC K4M had a profile similar to the commercial formulation. The release mechanism of theophylline from the formulations was described by Peppas's equation showing a non-Fickian release mechanism. The investigation of matrices swelling behavior showed that the gel layer thickness increased continuously over the time period studied. Moreover, a correlation between gel layer thickness and strength with the percentage released was found. CONCLUSIONS: These results suggest that melt granulation could be an easy and fast method to formulate sustained release tablets.

Chemistry, Pharmaceutical↗
PubMed2005

In vitro and in vivo evaluation of enoxaparin removal by continuous renal replacement therapies with acrylonitrile and polysulfone membranes.

BACKGROUND: Enoxaparin is a low-molecular-weight heparin for which the degree of elimination through hemofilters during continuous renal replacement therapy (CRRT) is not well established. OBJECTIVE: The elimination of enoxaparin by CRRT, using acrylonitrile (AN69) or polysulfone (PS) membranes, was studied in vitro and among critically ill patients. METHODS: In vitro procedures were carried out using Ringer's lactate, bovine albumin-containing Ringer's lactate, or fresh human plasma as enoxaparin vehicle, using AN69 or PS membranes, and following continuous veno-venous hemofiltration (CVVH) or continuous veno-venous hemodialysis (CVVHD). Prefilter and ultrafiltrate samples were collected over 60 minutes. All procedures were carried out in triplicate. Patients undergoing CRRT entered the in vivo study. Enoxaparin was administered subcutaneously once daily. The sieving coefficient (Sc) and saturation coefficient (Sa) were calculated as the relation between anti-factor Xa activity in simultaneously collected dialysate/ultrafiltrate samples and plasma samples. RESULTS: Mean Sc (for CVVH) or Sa (for CVVHD) values in the in vitro procedures ranged from 0.16 to 0.57. Sc values during CVVH were significantly higher than Sa values during CVVHD in the Ringer's lactate procedures for both membranes (AN69 membrane, P = 0.014; PS membrane, P < 0.001) and in the plasma procedures with the PS membrane (P < 0.001). Six male and 2 female patients (all white) participated in the in vivo study. Their mean body weight ranged from 55 to 80 kg, and their age ranged from 71 to 82 years. In patients, Sc or Sa achieved values between 0.26 and 0.67. No significant differences were found in vivo in the permeability of the 2 membranes to enoxaparin. CONCLUSIONS: In these studies, the Sc and Sa values suggested that enoxaparin passed through AN69 and PS membranes during CRRT. Further pharmacokinetic and clinical studies are needed to determine whether a dose adjustment for enoxaparin is needed for patients undergoing CRRT.

Acrylonitrile↗
PubMed2005

Influence of renal function on the pharmacokinetics of piperacillin/tazobactam in intensive care unit patients during continuous venovenous hemofiltration.

The pharmacokinetics of piperacillin/tazobactam (4 g/0.5 g every 6 or 8 hours, by 20-minute intravenous infusion) were studied in 14 patients with acute renal failure who underwent continuous venovenous hemofiltration with AN69 membranes. Patients were grouped according to severity (CL(CR) < or =10 mL/min, 10 < CL(CR) < or =50 mL/min, and CL(CR) > 50 mL/min). A noncompartmental analysis was performed. The sieving coefficient (0.78 +/- 0.28) was similar to the unbound fraction (0.65 +/- 0.24) for tazobactam, but it was significantly different (0.34 +/- 0.25) from the unbound fraction (0.78 +/- 0.14) for piperacillin. Extracorporeal clearance was 37.0% +/- 28.8%, 12.7% +/- 12.6%, and 2.8% +/- 3.2% for piperacillin in each group and 62.5% +/- 44.9%, 35.4% +/- 17.0%, and 13.1% +/- 8.0% for tazobactam. No patients presented tazobactam accumulation. In patients with CL(CR) < 50 mL/min, t(%)ss >MIC90 values were 100% for a panel of 19 pathogens, but in those with CL(CR) > 50 mL/min, t(%)ss >MIC90 indexes were 55.5% and 16.6% for pathogens with MIC90 values of 32 and 64. The extracorporeal clearance of piperacillin/tazobactam is clinically significant in patients with CL(CR) > 50 mL/min, in which the risk of underdosing and clinical failure is important and extra doses are required.

Aged↗
PubMed2005

Meropenem and continuous renal replacement therapy: in vitro permeability of 2 continuous renal replacement therapy membranes and influence of patient renal function on the pharmacokinetics in critically ill patients.

The pharmacokinetics of meropenem were characterized in 20 patients with different degrees of renal function who underwent continuous renal replacement therapy. Previously, no differences were detected in vitro in the removal of meropenem by continuous venovenous hemofiltration or continuous venovenous hemodialysis or when AN69 or polysulfone membranes were compared. In patients, no significant differences in the sieving coefficient or the saturation coefficient with the renal function were found, and the mean sieving coefficient/saturation coefficient value (0.80 +/- 0.12) was similar to the unbound fraction (0.79 +/- 0.08). An increase in total clearance and a decrease in elimination half-life were observed to the extent that the patient's creatinine clearance was higher. Likewise, the contribution of continuous renal replacement therapy to total clearance diminished in patients with less renal impairment. The results suggest that the renal function of the patient may influence meropenem pharmacokinetics during continuous renal replacement therapy. The lower trough plasma levels observed in nonrenal patients would not lead to adequate time during which serum drug concentrations are above the minimum inhibitory concentration values in many infections.

Acrylic Resins↗
PubMed2005

Pharmacokinetic/pharmacodynamic evaluation of antimicrobial treatments of orofacial odontogenic infections.

OBJECTIVE: To evaluate the efficacy of antimicrobial therapy in oral odontogenic infections using estimated pharmacokinetic/pharmacodynamic parameters or efficacy indices, and to compare pharmacokinetic/pharmacodynamic breakpoints with National Committee for Clinical Laboratory Standards' (NCCLS) breakpoints. STUDY DESIGN: Retrospective literature search to obtain minimum inhibitory concentration (MIC) values, pharmacokinetic parameters of antimicrobials and NCCLS breakpoints. Pharmacokinetic simulations were carried out using WinNonlin software (Pharsight Corporation, Mountain View, CA, USA). METHODS: For antimicrobials with time-dependent activity, the time that the plasma drug concentration exceeds the MIC as the percentage of dose interval at steady state was calculated. For antimicrobials with concentration-dependent activity, the total area under the plasma concentration-time curve over 24 hours at steady state divided by the MIC was calculated. Pharmacokinetic/pharmacodynamic breakpoints were calculated according to these parameters. RESULTS: Only amoxicillin/clavulanic acid and clindamycin showed adequate efficacy indices against the most commonly isolated bacteria in odontogenic infections. Metronidazole reached good indices against anaerobes only. Pharmacokinetic/pharmacodynamic susceptibility breakpoints do not coincide exactly with NCCLS breakpoints. CONCLUSION: Owing to the scarcity of double-blind, clinical trials on the use of antimicrobials in endodontics, this study may be useful in determining the best antimicrobial treatment in these infections. However, as we have not used concentration data in infected tissue to determine pharmacokinetic/pharmacodynamic indices, it would be necessary to design clinical trials in order to confirm these results.

Anti-Infective Agents↗
PubMed2004

The search for new beta-cell sources.

Type 1 diabetes affects an estimated 150 million people worldwide and results from an autoimmune-mediated destruction of insulin-producing beta-cells. In the United States alone more than 16 million people are affected by this disease and it is estimated that spending for diabetes management accounts for one out of every eight healthcare dollars. In this context, scientists are proposing novel therapeutic strategies that might allow a perfect glycemic control of most patients with diabetes.

Animals↗
PubMed2003

Cell microencapsulation technology for biomedical purposes: novel insights and challenges.

The aim of cell microencapsulation technology is to treat multiple diseases in the absence of immunosuppression. Using this technique, cells are immobilized within carefully designed capsules that allow the long-term function of the graft. Although the potential impact of this field is likely to be wide-ranging, the past few years have seen several 'firsts' that have brought the whole technology much closer to a realistic clinical application.

Animals↗
PubMed2003

Controversies over stem cell research.

Much interest and effort has focused on the therapeutic potential of stem cell technology to treat presently intractable diseases. However, this scientific promise has been accompanied by important issues, including ethical hurdles, political policies and dilemmas concerning cell-source selection (embryonic versus adult stem cells). Although the contribution of stem cells to medical research seems enormous, many countries now face complex ethical and regulatory questions, which could represent a significant limitation to medical progress and could take years to overcome.

Adult↗
PubMed2003

A glimmer of hope for diabetics?

Diabetes affects 150 million people worldwide and results from abnormal function of pancreatic islets. The scarcity of human tissue donors has focused interest in developing renewable sources of insulin-producing cells appropriate for engraftment. Advances in stem cell technology and transdifferentiation techniques have provided powerful tools to study pancreatic development, function and disease. Recent results from these two approaches could have significant implications for future therapies of diabetes.

Cell Differentiation↗
PubMed2002

Release of salbutamol sulphate and ketoprofen enantiomers from matrices containing HPMC and cellulose derivatives.

We studied the release of salbutamol and ketoprofen enantiomers from HPMC K100M matrices containing two types of cellulose derivatives: cellulose tris (3,5-dimethylphenylcarbamate) and cellulose tris (2,3-dichlorophenylcarbamate), chiral excipients used as stationary phases for liquid chromatography. These matrices provided an extended release of both drugs. Ketoprofen release from formulations elaborated with cellulose tris (2,3-dichlorophenylcarbamate) was by anomalous transport, because the value of n (release exponent of the diffusion equation) ranged between 0.60-0.68, whereas for all other formulations the value of exponent n ranged from 0.50-0.54. The drug thus diffuses through the matrix and is released following a quasi-Fickian diffusion mechanism (stereoselective process). The matrices preferentially retained R-salbutamol and S-ketoprofen and cellulose tris (3,5-dimethylphenylcarbamate) showed more capacity of chiral discrimination for both drugs than cellulose tris (2,3-dichlorophenylcarbamate). Moreover, we observed that stereoselectivity is dependent on the amount of chiral excipient in the formulation. Diffusion tests confirmed the chiral interaction between drugs and cellulose derivatives observed in the dissolution assays except for matrices elaborated with ketoprofen and cellulose tris (2,3-dichlorophenylcarbamate), where the low stereoselectivity observed with the matrices is due to the presence of HPMC K100M. We conclude that the inclusion of these cellulose derivatives in HPMC matrices does not result in a relevant stereoselectivity with respect to the two drugs studied.

Albuterol↗
PubMed2002

Encapsulated cell technology: from research to market.

Encapsulated cell technology has the potential to treat a wide range of diseases by the controlled and continuous delivery of biological products to the host. Many biotechnology companies have focused their interest in this technology taking into account the promising pre-clinical and clinical results and the potential clinical market. However, on the long way from clinic to market several issues will have to be addressed, including suitable scientific development, ethical obstacles, government regulations and market forces.

Biotechnology↗