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Biomedical subjects

P Marín

Publications and source records attributed to P Marín.

At least 19 recordsLinked to original sources

Pharmacokinetics and milk penetration of difloxacin after intravenous, subcutaneous and intramuscular administration to lactating goats.

The single-dose disposition kinetics of difloxacin were determined in clinically normal lactating goats (n = 6) after intravenous (i.v.), subcutaneous (s.c.) and intramuscular (i.m.) administration of 5 mg/kg. Difloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. The concentration-time data were analysed by compartmental and noncompartmental kinetic methods. Steady-state volume of distribution (V(ss)) and total body clearance (Cl) of difloxacin after i.v. administration were estimated to be 1.16 +/- 0.26 L/kg and 0.32 +/- 0.05 L/h x kg respectively. Following s.c. and i.m. administration difloxacin achieved maximum plasma concentrations of 1.33 +/- 0.25 and 1.97 +/- 0.40 mg/L at 3.37 +/- 0.36 and 1.79 +/- 1.14 h respectively. The absolute bioavailabilities after s.c. and i.m. routes were 90.16 +/- 11.99% and 106.79 +/- 13.95% respectively. Difloxacin penetration from the blood into the milk was extensive and rapid, and the drug was detected for 36 h after i.v. and s.c. dosing, and for 72 h after i.m. administration.

Animals↗

Pharmacokinetics and tissue tolerance of azithromycin after intramuscular administration to rabbits.

The pharmacokinetics of azithromycin after intravenous and intramuscular injection at a single dose rate of 10mg/kg bodyweight were investigated in rabbits by using a modified agar diffusion bioassay for determining plasma concentrations. The plasma creatine kinase activity was determined after i.m. administration for the evaluation of the tissue tolerance. The elimination half-lives of azithromycin after intravenous and intramuscular administration were 24.1 and 25.1h, respectively. After intramuscular administration mean peak plasma concentration was 0.26+/-0.01 mg/L and bioavailability was 97.7%. Plasma CK activity rose sharply within 8h after i.m. injection of azithromycin; activity returned to pre-treatment level by 48-72 h post-treatment. The transient rise in serum CK activity indicates some degree of muscle tissue damage at the injection site.

Animals↗

G-CSF increases the number of peripheral blood dendritic cells CD16+ and modifies the expression of the costimulatory molecule CD86+.

Dendritic cells (DC) play a key role in initiating immune reactions after allogeneic stem cell transplantation. The two main peripheral blood DC populations are myeloid (DC1) and lymphoplasmacytoid (DC2). A new subset of myeloid DC, expressing CD16, has been identified. We analyzed the number and CD86 expression of DC subsets in peripheral blood of 18 healthy donors, before and after granulocyte colony-stimulating factor (G-CSF) and in the inoculum of allogeneic peripheral blood transplants (allo-PBT; n=100) and allogeneic bone marrow transplants (allo-BMT; n=22). Granulocyte colony-stimulating factor administration increased the median number of DC1 (P=0.0007), of DC2 (P<0.0001) and of DC CD16+ (P=0.0001). Granulocyte colony-stimulating factor administration was also associated with a significant decrease of CD86 expression on DC1 (P=0.0003) and with a trend for an increase on DC CD16+ (P=0.07). Recipients of allo-PBT received similar quantities of DC1 and higher doses of DC2 and DC CD16+ than recipients of allo-BMT (P=0.5; P=0.0001; P<0.0001, respectively). Granulocyte colony-stimulating factor modifies the number of DC in peripheral blood and the expression of the costimulatory molecule CD86. This resulted in a different composition of DC2 and especially of DC CD16+ in the harvests, which might explain some of the differences observed in allogeneic reactions after allo-PBT with respect to allo-BMT.

Antibodies, Monoclonal↗

Stability of moxifloxacin injection in peritoneal dialysis solution bags (Dianeal PD1 1.36% and Dianeal PD1 3.86%).

BACKGROUND AND OBJECTIVE: Moxifloxacin is a new fluorquinolone with broad-spectrum activity. It is suitable for treating peritonitis in peritoneal dialysis (PD) patients. The objective of this study was to test stability of moxifloxacin in PD solutions stored at different temperatures. METHODS: Dialysis solution bags were used at two glucose concentrations; Dianeal PD1 1.36% and Dianeal PD1 3.86%. Moxifloxacin solution (2%) was injected into nine 2-L bags of Dianeal PD1 1.36% and nine bags of Dianeal PD1 3.86% under aseptic conditions to achieve a nominal concentration of 25 mg/L. Three bags of Dianeal PD1 1.36% and three bags of Dianeal PD1 3.86% were stored at each of three temperatures (4, 25 and 37 degrees C) and the same way for. Duplicate samples (2 mL) were taken at different times and precipitation, cloudiness, colour and pH was analysed. Moxifloxacin concentrations were measured using a modified HPLC method. RESULTS: The mean moxifloxacin concentration in the Dianeal PD1 1.36% solution remained > or =90% of the initial concentration for 14 days at 4 degrees C, 7 days at 25 degrees C and 3 days at 37 degrees C. For Dianeal PD1 3.86% moxifloxacin concentrations remained > or =90% for 14 days at 4 degrees C, 3 days at 25 degrees C and 12 h at 37 degrees C. CONCLUSIONS: Moxifloxacin shows sufficient stability in both PD bags for use in PD patients.

Anti-Infective Agents↗

Pharmacokinetics of moxifloxacin in rabbits after intravenous, subcutaneous and a long-acting poloxamer 407 gel formulation administration.

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long-acting poloxamer 407 gel formulation (SC-P407). Moxifloxacin concentrations were determined by high-performance liquid chromatography assay with fluorescence detection. Mean half-life for IV, SC and SC-P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C(max) was 1.61 +/- 0.49 mg/l. After SC-P407 administration, the bioavailability was 44% and the C(max) 1.83 was +/-0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC-P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC-P407 formulation and the favourable PK behaviour such as the long half-life, acceptable bioavailability and excellent PK-PD ratios achieved indicate that it is likely to be effective in rabbits.

Animals↗

Pharmacokinetics of danofloxacin in horses after intravenous, intramuscular and intragastric administration.

REASONS FOR PERFORMING STUDY: Danofloxacin is a fluoroquinolone developed for veterinary medicine showing an excellent activity. However, danofloxacin pharmacokinetics profile have not been studied in horses previously. OBJECTIVE: To study the pharmacokinetics following i.v., i.m. and intragastric (i.g.) administration of 1.25 mg/kg bwt danofloxacin to 6 healthy horses. METHODS: A cross-over design was used in 3 phases (2 x 2 x 2), with 2 washout periods of 15 days (n = 6). Danofloxacin (18%) was administered by i.v. and i.m. routes at single doses of 1.25 mg/kg bwt. For i.g. administration an oral solution was prepared and administered via nasogastric tube. Danofloxacin concentrations were determined by HPLC assay with fluorescence detection. Tolerability at the the site of i.m. injection was monitored by creatine kinase (CK) activity. RESULTS: Danofloxacin plasma concentration vs. time data after i.v. and i.g. administration could best be described by a 2-compartment open model. The disposition of i.m. administered danofloxacin was best described by a one-compartment model. The terminal half-lives for i.v., i.m. and i.g. routes were 6.31, 5.36 and 4.74 h, respectively. Clearance value after i.v. dosing was 0.34 l/kg bwt/h. After i.m. administration, absolute bioavailability was mean +/- s.d. 88.48 +/- 11.10% and Cmax was 0.35 +/- 0.05 mg/l. After i.g. administration, absolute bioavailability was 22.36 +/- 6.84% and Cmax 0.21 +/- 0.07 mg/l. CK activity following i.m. dosing increased 3-fold over pre-injection levels 12 h after dosing and subsequently approached (but did not reach) normal values at 72 h post dose. CONCLUSIONS: Systemic danofloxacin exposure achieved in horses following i.m. administration was consistent with the predicted blood levels needed for a positive therapeutic outcome for many equine infections. Conversely, danofloxacin utility by the i.g. route was limited by low bioavailability. Tolerability associated with i.m. administration was high. POTENTIAL RELEVANCE: Pharmacokinetics, blood levels and good tolerability of i.v. and i.m. administration of danofloxacin in horses indicates that it is likely to be effective for treating sensitive bacterial infections.

Animals↗

SPE-GC-MS for the sampling and determination of unmetabolized styrene in urine.

The urinary excretion of unmetabolized styrene can be a very good indicator for biomonitoring styrene in occupationally exposed people. The use of a new urine sampling system, involving a solid-phase extraction cartridge, offers several advantages for determining styrene. The advantages are especially related to the pre-analytical phase of styrene determination, which may be influenced by many variables. The effect on styrene recovery of sorbent type, eluting solvent, elution volume, elution flow-rate, and the addition of methanol to the washing solvent, was evaluated by experimental design methodology. As a result, Oasis HLB cartridges were selected for urine sampling, as well as 1.5 mL of ethyl acetate at 0.5 mL/min for eluting the retained styrene. These conditions were then applied to the validation of the solid-phase extraction combined with GC-MS method for the sampling and analysis of unmetabolized styrene in urine. The overall uncertainty was in the 12-22% range and the limit of detection was 2.2 microg/L for a 4 mL urine sample. The stability of styrene has been studied both in cartridges and in vials under different storage periods. After 1 month period the styrene stored on cartridges at room temperature remained stable, whereas this is not the case for styrene recovery from vials. The results obtained indicate that on-site solid-phase extraction of urine can provide a simple, accurate and reproducible sampling and analytical method for the biomonitoring of styrene in urine.

Chromatography, Liquid↗

Smoking habit and genetic factors associated with lung cancer in a population highly exposed to arsenic.

In order to find some relationship between genetic differences in metabolic activation and detoxification of environmental carcinogens and host susceptibility to chemically induced cancers, we have investigated the distribution of the GSTM1 null genotype and CYP450 *1A1 MspI polymorphism in lung cancer patients and healthy volunteers of the second region in the north of Chile highly exposed to arsenic. The main sources of environmental arsenic exposure in Chile are copper smelting and drinking water, specially in the second region, the most important copper mining region in the world that shows the highest lung cancer mortality rate in the country (35/100.00). The population of Antofagasta, the main city of the region was exposed between 1958 and 1970 to arsenic concentrations in drinking water of 860 microg/m3, presently declining to 40 microg/m3. For men the MspI CYP1A1 *2A genotype was associated with a highly significant estimated relative lung cancer risk (O.R. = 2.60), but not GSTM1 by itself. The relative lung cancer risk for the combined 2A/null GSTM1 genotypes was 2.51, which increased with the smoking habits (O.R. = 2.98). In the second region the cancer mortality rate for As associated cancers, might be related at least part to differences in As biotransformation. In this work we demonstrate that genetic biomarkers such as CYP1A1 2A and GSTM1 polymorphisms in addition to DR70 as screening biomarkers might provide relevant information to identify individuals with higher risk for lung cancer, due to arsenic exposure.

Adult↗

CYP1A1 and GSTM1 genetic polymorphisms in lung cancer populations exposed to arsenic in drinking water.

Region II of Chile is the most important copper mining area in the world and it shows the highest lung cancer mortality rate in the country (35/100,000). The population in Antofagasta, the main city of Region II, was exposed from 1958 to 1970 to 860 microg m(-3) arsenic (As) in drinking water and has currently been declining to 40 microg m(-3). Glutathione serves as a reducing agent and glutathione S-transferase (GST) may have an important role in As methylation capacity and body retention. In the current study, the null genotype of GSTM1 and the MspI polymorphism of CYP450 1A1 were investigated in lung cancer patients and in healthy volunteers of Region II. In males, the 2A genotype of MspI represented a highly significant estimated relative lung cancer risk (OR=2.60). Relative lung cancer risk for the combined 2A/null GSTM1 genotypes was 2.51, which increased with the smoking habit (OR=2.98). In Region II, the cancer mortality rate for As-associated cancers at least partly might be related to differences in As biotransformation. Genetic biomarkers such as 2A and GSTM1 polymorphisms in addition to DR70 as screening biomarkers might provide relevant information to identify individuals with a high risk for lung cancer as prevention and protection actions to protect public health.

Arsenic↗

Pharmacokinetics of azithromycin after i.v. and i.m. administration to sheep.

The pharmacokinetics (PK) of azithromycin after i.v. and i.m. injection at a single dosage of 20 mg/kg bodyweight was studied in sheep. Blood samples were collected from the jugular vein until 120 h after dosing for both routes. Plasma concentrations of azithromycin were determined by bioassay. The plasma concentration-time data of azithromycin best fitted a three-compartment model after i.v. administration and a two-compartment model with first-order absorption after i.m. administration. The elimination half-life (t(1/2lambdaz)) was 47.70 +/- 7.49 h after i.v. administration and 61.29 +/- 13.86 h after i.m. administration. Clearance value after i.v. dosing was 0.52 +/- 0.08 L/kg.h. After i.m. administration a peak azithromycin concentration (C(max)) of 1.26 +/- 0.19 mg/L was achieved at 1.24 +/- 0.31 h (t(max)). Area under the curve (AUC) were 38.85 +/- 5.83 mg.h/L and 36.03 +/- 1.52 mg.h/L after i.v. and i.m. administration respectively. Bioavailability obtained after i.m. administration was 94.08 +/- 11.56%. The high tolerability of this i.m. preparation and the favourable PK behaviour such as the long half-life and high bioavailability make azithromycin likely to be effective in sheep.

Animals↗

Clinical and MRI outcome after autologous hematopoietic stem cell transplantation in MS.

The authors report the outcome of 14 patients with severe multiple sclerosis treated with autologous hematopoietic stem cell transplantation (AHSCT) after a median follow-up period of 3 years. The 3-year actuarial probability of progression-free survival was 85.7% and that of disease activity-free survival was 46.4%. On MRI, no T1-enhanced lesions were detected after AHSCT. The mean change in T2 lesion volume from baseline to the third year was -20.2% and that of the corpus callosum area was -12.7%; 50% of this reduction was seen during the first year.

Actuarial Analysis↗

[Antifungal susceptibility of Acremonium species using E-test and Sensititre].

Filamentous fungi have become a common cause of severe infections, especially in immunocompromised patients. In recent years, the number and diversity of the infections caused by Acremonium species have increased and numerous species have been implicated. As is the case for most emerging pathogens, the optimal therapeutic approach to Acremonium species remains to be determined. We used two methods to determine the in vitro susceptibility to amphotericin B, itraconazole and fluconazole for 15 clinical isolates of eight different species of Acremonium. The MICs were determined according to protocol M38-A of the National Committee for Clinical Laboratory Standards (NCCLS) document, using the Sensititre and E-test microdilution methods. Amphotericin B was effective in vitro for few species using the Sensititre method. However, high MICs were obtained with E-test. Fluconazole and itraconazole were ineffective according to both methods. Acremonium species are generally resistant to the most commonly used antifungal agents. Consequently, Acremonium susceptibility testing is recommended to assist in choosing adequate treatment of infections caused by this filamentous fungus.

Acremonium↗

Three-dimensional mesh for ventral hernias: a new technique for an old problem.

The morbidity/mortality associated with ventral hernias continues to be a serious medical problem due to high rates of recurrence. Meshes offer a simple and effective solution and, bearing this in mind, we describe a new protocol developed in our department, which consists of dissecting the hernia to free the peritoneal space, in which the three-dimensional mesh (PHS) is lodged. From July 1999-November 2002, this technique was used in 32 adult and elderly patients: four eventrations caused by trocars, seven eventrations from laparotomy, 14 umbilical hernias, five epigastric hernias, and two spigelian hernias. The size of the hernial ring was 10 cm or less in all cases. All patients underwent surgery under spinal anaesthesia and with antibiotic prophylaxis. No patient required readmission, experienced infection of the mesh or recurrence, or required more oral analgesia than prescribed on discharge. The mean hospital stay was 30+/-15 h, and only five of 32 patients required more than 1 day of stay. No deaths occurred. Therefore, we think that the use of the PHS mesh in ventral hernia is a safe, effective, and simple technique.

Adult↗

Application of solid-phase microextraction and gas chromatography-mass spectrometry to the determination of volatile organic compounds in end-exhaled breath samples.

Analysis of exhaled air is of particular interest as an indicator of health as well as a tool for the diagnosis of diseases. It is also a very attractive procedure for the biological control of the exposition to hazardous solvents. This kind of analysis presents numerous advantages over other methods, the most important being that it is not an invasive procedure and, therefore, it is well accepted and can be applied to a wide range of compounds. Furthermore, the analysis is simplified since the matrix is less complex that in the case of blood or urine. In spite of these obvious advantages and the good results obtained, analysis of exhaled air is not in daily use, probably due to the fact that there are no normalized systems of sampling, thus making the interpretation of the results difficult. In this paper, a method for the determination of tetrachloroethylene in exhaled air using solid-phase microextraction is presented. This method, which can be applied to other volatile organic compounds, was developed with special emphasis of end-exhaled breath sampling. The sample is collected in a glass tube whose ends are closed once the exhalation is finished. The tube has an orifice sealed with a septum through which the fiber is inserted. Then, the fiber is desorbed in the injector of a gas chromatograph and the analysis is accomplished using mass spectrometry for the identification and quantification of the components. The proposed system avoids the need of complex sampling equipment and allows analysis of the alveolar fraction. Additionally, the system is economical and easy to handle, thus facilitating the development of normalized methods and its routine use in field studies.

Breath Tests↗

CsA-based post-graft immunosuppression: the main factor for improving outcome of allografted patients with acquired aplastic anemia. A retrospective survey by the Spanish Group of Hematopoietic Transplantation.

A retrospective multicenter study was performed to assess the clinical results in patients with acquired aplastic anemia (AA) allografted over a 19 year period and to identify prognostic factors influencing survival. From April 1978 to December 1997, 176 patients were transplanted. Records from 160 receiving related matched bone marrow transplantation (BMT) were reviewed. Fifty-two percent of the patients were older than 20 years, 5% older than 40; 6.3% were untransfused at BMT and 56.2% had received prior treatments. Conditioning regimens were with chemotherapy in 43.7% of the procedures and with additional irradiation in 56.3%. Graft-versus-host disease (GVHD) prophylaxis was based on cyclosporin A (CsA) in 58.1% of the patients while methotrexate (MTX) was administered to 41.9%. Transplantation earlier on, a longer interval from diagnosis to BMT, GVHD prophylaxis with MTX, graft failure/rejection and acute severe GVHD were adverse factors for survival. The use of CsA emerged as the main factor for the improvement, inducing a significant decrease in graft failure/rejection rate and severe acute GVHD when compared with MTX alone. Radiation-containing regimens decreased the graft failure/rejection rate without improving survival due to the increased risk of acute GVHD. Age and number of transfusions pretransplant did not influence outcome. Survival achieved since 1991 is 79.79%, and graft failure and acute severe GVHD rates are 6.0% and 11.8%, respectively. In conclusion, CsA-based post-graft immunosuppression has been crucial in achieving improved survival in patients with acquired AA up to 40 years of age. Regardless of CsA use, further improvement in survival was apparent with time, probably due to better skills in patient care.

Adolescent↗

[Study of the susceptibility of black yeasts of the Exophiala genus to antifungals using the Sensititre System].

Black yeasts belong to a group of dematiaceous fungi which are difficult to classify and identify. One of the genera that cause human infection, mainly phaeohyphomycosis, is Exophiala, which includes the species E. berger, E. castellanii, E. dermatitidis, E. jeanselmei, E. lecanii-corni, E. moniliae, E. pisciphila, E. salmonis and E. spinifera. We carried out a susceptibility study of five of these species (E. castellanii, E.dermatitidis, E, jeanselmei, E. lecanii-corni and E. moniliae), isolated from cutaneous exudates, to the usual antimycotic agents. Strains were cultured on Sabouraud agar and potato-dextrose agar. Species identification was made by conidiogenous microscopic observation and the following characteristics: maximum growth temperature, tolerance to cicloheximide and carbohydrate assimilation. Susceptibility to antimycotic agents (amphotericin B, fluconazole, itraconazole, ketoconazole and 5-fluorocytosine) was determined by the Sensititre YeastOne (Aamar Blue) commercial method. Amphotericin B activity was good for the five tested species, although the MIC for E. jeanselmei was high (1 mg/l. MICs for fluconazole were high for all the species, but only E. moniliae and E. lecanii-corni c be considered resistant. Activity of itraconazole, ketoconazole and 5-fluorocytosine was good.

Antifungal Agents↗

[Bioartificial liver support for acute liver failure. First case treated in Spain].

BACKGROUND: Research aimed at developing artificial liver support systems has experienced a notable increase in the last decade. Hybrid systems including bioreactors containing hepatocytes which are perfused by liver failure patients blood or plasma have been deviced for the first time. The purpose of such a strategy is to substitute, at least in part, the impaired hepatic function thus improving the prognosis of patients with severe acute or chronic liver diseases. CASE REPORT: In the present paper, we report the first such a case treated in Spain in the context of a controlled, randomized, multicenter international study aimed at investigating the usefulness and safety of a bioartificial liver support system based on cryopreserved porcine hepatocytes in patients with acute liver failure or having a non-functioning primary graft after liver transplantation. RESULTS: In this first experience, two sessions of treatment could be completed before a patient with acute liver failure underwent a successful emergency liver transplantation. After more than two years of follow-up, the patient is in her normal life activities and she has not presented any adverse event related to the bioartificial liver support therapy so far. CONCLUSION: Bioartificial liver support systems are starting to be available for use in clinical practice. Yet it is mandatory to establish their safety and efficacy before a widespread recommendation.

Acute Disease↗