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Biomedical subjects

M Watts

Publications and source records attributed to M Watts.

At least 19 recordsLinked to original sources
PubMed2007

Antimicrobial peptide modulation in a differentiated reconstructed gingival epithelium.

Gingival innate immunity has been studied by using biopsies and normal or transformed epithelial cell monolayers. To overcome individual biological variabilities and as a physiological alternative, we have proposed using a reconstructed tissue equivalent. In this study, we investigated the functionality and the stage of differentiation of a reconstructed human gingival epithelium. We also characterized this epithelium at the molecular level to investigate its differentiation stage compared with native human gingival epithelium. The expression levels and localization of markers related to proteins and lipids of well-differentiated stratified epithelium, such as cytokeratins, cornified envelope proteins and enzymes, or to factors in lipid synthesis and trafficking were examined. Immunohistochemistry revealed similar localization patterns in both types of epithelia and mRNA quantification showed a close resemblance of their expression profiles. We further revealed that, like native gingiva, reconstructed gingival epithelium was able to respond to pro-inflammatory or lipopolysaccharide stimuli by producing antimicrobial peptides hbetaD-2, hbetaD-3 or LL-37. Finally, we demonstrated that reconstructed human gingival epithelium, as a model, was good enough to be proposed as a functional equivalent for native human gingival epithelium in order to study the regulation of gingival innate immunity against periodontal infections.

Antimicrobial Cationic Peptides↗
PubMed2006

Endocapsular iris reconstruction implants for acquired iris defects: a clinical study.

PURPOSE: To report the clinical efficacy, safety, and long-term follow-up data on the use of endocapsular iris reconstruction implants (IRIs) during cataract surgery in patients with acquired iris defects. METHODS: Single centre, retrospective, noncomparative, interventional case series. Five eyes of four patients with acquired iris defects and visually significant cataracts underwent clear cornea phacoemulsification and intraocular lens (IOL) implantation combined with insertion of endocapsular IRI. Data on the best-corrected visual acuity (BCVA), degree of preoperative and postoperative glare, photophobia, surgical complications, and long-term implant stability were analysed. RESULTS: In all patients, IRI were successfully placed within the capsular bag during cataract surgery. There were no intraoperative or postoperative complications. Mean follow-up period was 29 months (range, 16-42). BCVA, subjective glare, and photophobia improved in all five eyes. Desired anatomic results were achieved in all of them. CONCLUSIONS: In patients with acquired iris defects, implantation of endocapsular IRI during cataract surgery appears to be a safe and effective procedure. At a mean time gate of 29 months, both IOLs and IRI appeared to remain stable within the capsular bag.

Adult↗
PubMed2006

[Wound healing effect of Eludril in a model of human gingival mucosa].

INTRODUCTION: The aim of this study was to evaluate and to compare the potential for wound healing of the buccal mucosa with the use of two mouth rinses; one containing 0.10% chlorhexidine with alcohol, the second containing 0.12% chlorhexidine without alcohol. MATERIAL AND METHOD: Using a model of human buccal mucosa kept alive ex vivo, an immunohistochemical assessment of the mitotic potential of epithelial cells and a biochemical evaluation of the capacity of the fibroblasts of the gingival mucosa to synthesize collagen was performed. RESULTS: A mouth rinse containing 0.10% chlorhexidine with alcohol (Eludril) did not alter the potential for epithelial proliferation and for collagen synthesis within the gingival chorion grown in survival conditions. The results revealed a significant difference between the two mouth rinses for each of the parameters studied. The most favourable results were obtained with the mouth rinse containing alcohol. DISCUSSION: The presence of alcohol in a mouth rinse containing 0.10% chlorhexidine has no deleterious effects on healing capacity. On the contrary, it helps stimulate wound healing. The combination of chlorhexidine plus alcohol is superior for healing, chlorhexidine alone does not show any significant difference compared with the control.

Anti-Infective Agents, Local↗
PubMed2006

Abnormal haemoglobin levels in acute coronary syndromes.

BACKGROUND: Anaemia is an adverse prognostic marker in acute coronary syndromes (ACS), but the epidemiology of abnormal haemoglobin levels in such patients is uncertain. AIMS: To investigate the prevalence, nature and predictors of abnormal haemoglobin levels in ACS patients at admission. DESIGN: Observational study. METHODS: All emergency admissions from January to April 2005 were assessed within 24-48 h of hospital admission. ACS patients (unstable angina, non-ST-elevation or ST-elevation myocardial infarction) were enrolled (n = 320, 190 men). Clinical information was recorded. RESULTS: Overall, 71% had unstable angina; 18% non-ST-elevation myocardial infarction (MI), and 11% ST-elevation MI. Mean +/- SD haemoglobin was 14.3 +/- 1.7 g/dl in men and 13.2 +/- 1.5 g/dl in women. Abnormal haemoglobin was more common in men (65, 34%) than in women (34, 22%) (p = 0.013). Anaemia (haemoglobin <13 g/dl in men, or <12.0 g/dl in women) was recorded in 35 (18%) men and 24 (18%) women. All had admission haemoglobin >8 g/dl, and anaemia was usually normocytic. Multivariate predictors of anaemia (OR, 95%CI) were age (1.07, 1.04-1.1) and serum albumin (0.90, 0.81-1.00). Elevated haemoglobin (>16 g/dl) was recorded in 30 (16%) men and 4 (3%) women (p < 0.01), and was more common in ST-elevation MI patients (26%) than in unstable angina or non-ST elevation MI patients (9%) (p = 0.005). In patients who underwent invasive management with a post-procedure haemoglobin the following day (n = 85), 15 (18%) new cases of anaemia were detected. Admission duration correlated with haemoglobin (p < 0.01), creatinine (p < 0.01), troponin I (p < 0.01) and C-reactive protein (p < 0.01). Anaemia was more common in those who died in hospital (3, 60%) than in those who survived (56, 18%) (adjusted p = 0.0135). DISCUSSION: Abnormal haemoglobin levels were common in our ACS admissions. Anaemia was generally mild. Increasing age and interventional management were associated with anaemia, which in turn was associated with adverse in-hospital outcomes. Interventions to prevent and detect anaemia in this setting merit prospective testing.

Anemia↗
PubMed2006

Evaluation of the inclusion of soybean oil and soybean processing by-products to soybean meal on nutrient composition and digestibility in swine and poultry.

This experiment was designed to evaluate the effects of selected soybean (SB) processing byproducts (gums, oil, soapstock, weeds/trash) when added back to soybean meal (SBM) during processing on the resulting nutrient composition, protein quality, nutrient digestibility by swine, and true metabolizable energy (TMEn) content and standardized AA digestibility by poultry. To measure ileal DM and nutrient digestibility, pigs were surgically fitted with a T-cannula in the distal ileum. The concentration of TMEn and the standardized AA digestibility by poultry were determined using the precision fed cecectomized rooster assay. Treatments in the swine experiment included SBM with no by-products; SBM with 1% gum; SBM with 3% gum; SBM with 0.5% soapstock; SBM with 1.5% soapstock; SBM with 2% weeds/trash; SBM with a combination of 3% gum, 1.5% soapstock, and 2% weeds/trash; SBM with 5.4% soybean oil; and roasted SB. A 10 x 10 Latin square design was utilized. The experiment was conducted at the University of Illinois, Urbana-Champaign, and at The Ohio State University, Columbus. In the swine experiment, apparent ileal DM, OM, CP, and AA digestibilities were reduced (P < 0.05) when pigs consumed the combination by-product diet compared with the diet containing no by-products. Apparent ileal digestibilities of DM, CP, and total essential, total nonessential, and total AA were lower (P < 0.05) for any diet containing by-products compared with the diet with no by-products. Apparent ileal digestibilities of DM, OM, CP, and AA were lower (P < 0.05) for the roasted SB-compared with the SB oil-containing diet. In the rooster experiment, TMEn values were greater (P < 0.05) for roasted SB compared with SBM with no by-products and increased linearly as the addition of soapstock increased. Individual, total essential, total nonessential, and total AA digestibilities were lower (P < 0.05) for roosters fed roasted SB versus SBM devoid of by-products. Gums, soapstock, and weeds/trash reduce the nutritive value of the resultant meal when they are added back during processing.

Animal Feed↗
PubMed2005

Differential effects of temperature and maturity stage on hepatic estrogen receptor characteristics of Atlantic salmon.

In order to determine if elevated temperature during vitellogenesis had a detrimental effect on hepatic estrogen receptors of Atlantic salmon (Salmo salar), 3H-estradiol saturation binding analysis, using one- and two-site binding models, was carried out on extracts of hepatic cytosols from fish held at 14, 18 or 22 degrees C over the austral period of peak vitellogenesis (February to April). With one-site binding analysis, no temperature related difference in either receptor affinity (Kd) or number (Bmax) was found at each sampling point, but there was an apparent decrease in both affinity and number at each temperature over the period of the study. However, some analyses, notably at 22 degrees C during February, were best described using a two-site binding model. At this temperature and time, there was a clear separation of binding affinity into high and low components (Kd = 0.67+/-S.E. 0.05 and 20+/-S.E. 5.6 nM, respectively) (n = 4), which suggests that February was a critical time of temperature related hepatic sensitivity to estrogen. These results support those of other studies where we found that February was also a sensitive time with respect to temperature impairment of in vitro follicular estrogen synthesis, and the greatest period of in vivo temperature sensitivity.

Aging↗
PubMed2004

Ileal amino acid digestibilities by pigs fed soybean meals from five major soybean-producing countries.

Growing conditions and processing technologies to which soybeans (SB) are exposed have an effect on digestibilities of AA found in the resultant soybean meals (SBM). This study evaluated SBM from five major SB-producing countries (Argentina, Brazil, China, India, and the United States). An industry representative in each country collected samples of unprocessed SB and SBM subjectively determined to be of high, intermediate, or low quality. The SB from each country were processed into SBM under uniform conditions in the United States. Five experiments (each examining the three SBM and the SB processed in the United States from a single country) were conducted to determine true ileal AAd digestibilities. In addition, a standard SBM purchased on the open market in the United States was used in all experiments as a control. Data from pigs fed a low-protein casein diet in each study were used to calculate true AA digestibilities. Pigs were fitted with simple T-cannulas at the terminal ileum and allotted to treatments in Latin square design experiments. Duplicate experiments were conducted at the University of Illinois and at The Ohio State University. Within each country comparison, pigs fed the SBM processed in the U.S. from SB grown in the five countries had lower (P < 0.05) true total amino acid (TAA) digestibilities than did pigs fed any of the SBM prepared within the country of origin, except the United States. This indicates that processing conditions used at the U.S. pilot plant were not ideal when using SB from other countries. True TAA digestibilities of the diets containing the high-, intermediate-, and low-quality SBM did not differ, except for China, where the low-quality SBM (83.5%) had a lower (P < 0.05) digestibility than the intermediate- (89.6%) or high- (89.0%) quality meals. Soybean meal produced in Argentina (average, 87%) and Brazil (average, 82%) had lower (P < 0.05) true TAA digestibilities than did the standard SBM (91%), indicating that the processing plants in those countries may produce a less digestible SBM than that available on the open market in the United States.

Agriculture↗
PubMed2003

Identification of endocrine-disrupting effects in aquatic vertebrates and invertebrates: report from the European IDEA project.

The EU-funded project IDEA aimed to evaluate (a) what parameters and endpoints allow the detection of endocrine-mediated developmental and reproductive effects of (xeno)estrogens in life cycle- and life stage-specific toxicity tests with the zebrafish Danio rerio, a small laboratory fish used in many ecotoxicity test guidelines, and (b) whether substances that act as estrogens in vertebrates may also adversely affect the development, differentiation, and reproduction of aquatic invertebrates. The invertebrate species investigated included Hydra vulgaris, Gammarus pulex, Chironomus riparius, Hyalella azteca, and Lymnaea stagnalis. The animals were exposed to the model estrogenic chemicals ethynylestradiol (EE2), bisphenol A (BPA), and octylphenol (OP), which exert their endocrine activity in vertebrates through the estrogen receptor. As endpoints, developmental and reproductive parameters at the organism level as well as molecular and cellular parameters were measured. Life cycle exposure of zebrafish to (xeno)estrogens induced a specific, partly irreversible response pattern, consisting mainly of (a) induction of vitellogenin (VTG), (b) alterations of gonad differentiation, (c) delay of first spawning, and (d) reduced fertilization success. The effects of EE2 on zebrafish were expressed at environmentally realistic concentrations, while BPA and OP became effective at concentrations higher than those usually found in the environment. The vitellogenic response was equally sensitive as the reproductive parameters in the case of EE2, but VTG was more sensitive in the case of BPA. Partial life cycle exposure of zebrafish had lasting effects on fish development and reproduction only when the fish were exposed during the stage of juvenile bisexual gonad differentiation. In (partial) life cycle and multigeneration studies with invertebrates, (xeno)estrogenic impact was assessed by a range of developmental and reproductive parameters including hatching, growth, moulting, mating behavior, and egg number. Several parameters were found to be responsive to (xeno)estrogens; however, most effects were induced only at higher, probably nonphysiological concentrations. Low-dose effects were observed in full life cycle experiments, particularly in the second generation. It remains to be established whether the estrogen-induced alterations in the invertebrate species indeed do result from disturbances of the endocrine system. The findings of the present research project support the development of appropriate testing methodologies for substances with estrogenic activity.

Animals↗
PubMed2003

Vitellogenin isolation, purification and antigenic cross-reactivity in three teleost species.

Vitellogenin (Vtg) was isolated from male greenback flounder (Rhombosolea tapirina), rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar) plasma, following induction by estradiol (E(2)) inoculation. The molecular weight of each native molecule, as determined by gel filtration, was 540, 383 and 557 kDa, respectively. With sodium dodecyl sulphate polyacrylamide gel electrophoresis under reducing conditions, Atlantic salmon and greenback flounder Vtg appeared as three major bands (approximately 159, 117, 86 kDa and 155, 104, 79 kDa, respectively), whereas rainbow trout Vtg appeared as one major band (approximately 154 kDa). Several minor bands were also present in each Vtg isolate. Polyclonal antisera, produced against only the highest molecular weight band from each species following excision from reducing gels, were reactive with all major bands in Western blots. In competition ELISA, parallel binding slopes were demonstrated between purified Vtg and plasma from vitellogenic females of the same species, but there was no reaction with plasma from untreated males. These antisera were highly species-specific and little cross-reactivity was noted, even between the two salmonid species. These data suggest that excision of bands from gels is a simple procedure for the preparation of species-specific antisera, and confirm that cross-species assays give highly variable results.

Animals↗
PubMed2001

Isolation and partial characterisation of immunoglobulin from southern bluefin tuna Thunnus maccoyii Castelnau.

Specific and total serum immunoglobulins were extracted by immunoaffinity, mannan-binding protein and Protein A affinity chromatography from southern bluefin tuna (Thunnus maccoyii Castelnau) immunised with rabbit IgG, and from non-immunised southern bluefin tuna. SDS-PAGE in 10% reducing gels revealed two heavy chains with molecular weights of approximately 74.6 +/- 1.3 kDa and 71.2 +/- 0.9 kDa, and two light chains with molecular weights of approximately 29 +/- 1.2 kDa and 28 +/- 1.0 kDa. Under non-reducing, but denaturing, conditions in 4% and 5% SDS-PAGE gels, a high molecular weight and a low molecular weight fraction were demonstrated. By gel filtration using Sephacryl HR 300 a molecular weight of 845 kDa, consistent with a tetramer, was obtained for the high molecular weight fraction, and a molecular weight of 168 kDa, consistent with a monomer, was obtained for the low molecular weight fraction. The extinction coefficient at A280 for the purified immunoglobulin (Ig) was determined to be 1.24. Tuna a-rabbit IgG Ig was reactive with all non-reduced mammalian IgG antigens tested, suggesting that common conformational antigenic determinants were recognised.

Animals↗
PubMed2001

Immune responses of teleost fish.

In fish all the pre-requisites to mount a specific immune response are present, but the main differences from the mammalian system are that the secondary response is relatively minor and IgG is not present. In teleosts mainly IgM is present, and IgD has been recently described but its function is, as yet, unknown. However, different forms of fish IgM and its observed flexibility of structure may compensate for a lack of Ig class diversity. The innate immune response of teleosts is highly developed. Multiple forms of key constitutive and inducible components, such as lysozyme, C3, alpha2-macroglobulin and C-reactive protein, are present, and may enhance immune recognition. Low ambient temperature appears to have an impact on all aspects of the immune response, particularly the T-dependent specific immune response due to the non-adaptive lipid composition of T-cell membranes. Temperature effects on the nonspecific immune system are less well characterised, but there is evidence that low temperatures are also suppressive. Knowledge of immune system function becomes essential for disease prevention strategies such as the development of vaccines, selection for increased disease resistance and identification of genes suitable for trangenesis.

Animals↗
PubMed2000

Effect of changes in expression of the amphotropic retroviral receptor PiT-2 on transduction efficiency and viral titer: implications for gene therapy.

The aim of this study was to quantify the impact of amphotropic retroviral receptor (PiT-2) levels on susceptibility to transduction and to determine whether the low level of PiT-2 found on CD34+ hematopoietic cells is within the range likely to compromise gene transfer. Receptor-deficient Chinese hamster ovary (CHO) cells were transfected with a PiT-2 construct that could be induced by the removal of tetracycline. The level of PiT-2 expression measured by virus binding in uninduced and in fully and partially induced transfectants correlated with the efficiency of transduction by an amphotropic retroviral reporter vector. Fully induced CHO-PiT-2 cells gave apparent viral titers similar to NIH 3T3 fibroblasts while addition of tetracycline reduced titers by up to 140-fold. Binding of the same vector preparation to purified CD34+ peripheral blood stem cells (PBSCs) was always less than to uninduced CHO-PiT-2 transfectants even after preincubation in 10-ng/ml concentrations of IL-3, IL-6, and stem cell factor, which increased retroviral binding by an average of 35%. The level of expression of the amphotropic retroviral receptor PiT-2 thus significantly limits transduction efficiency within the range observed in target cells of importance in human gene therapy.

3T3 Cells↗
PubMed1999

Intravascular extraction of problematic or infected permanent pacemaker leads: 1994-1996. U.S. Extraction Database, MED Institute.

Of the 400,000-500,000 permanent pacemaker leads implanted worldwide each year, around 10% may eventually fail or become infected, becoming potential candidates for removal. Intravascular techniques for removing problematic or infected leads evolved over a 5-year period (1989-1993). This article analyzes results from January 1994 through April 1996, a period during which techniques were fairly stable. Extraction of 3,540 leads from 2,338 patients was attempted at 226 centers. Indications were: infection (27%), nonfunctional or incompatible leads (25%), Accufix or Encore leads (46%), or other causes (2%). Patients were 64+/-17 years of age (range 5-96); 59% were men, 41% women. Leads were implanted 47+/-41 months (maximum 26 years), in the atrium (53%), ventricle (46%), or SVC (1%). Extraction was attempted via the implant vein using locking stylets and dilator sheaths, and/or transfemorally using snares, retrieval baskets, and sheaths. Complete removal was achieved for 93% of leads, partial for 5%, and 2% were not removed. Risk of incomplete or failed extraction increased with implant duration (P<0.0001), less experienced physicians (P<0.0001), ventricular leads (P<0.005), noninfected patients (P<0.0005), and younger patients (P<0.0001). Major complications were reported for 1.4% of patients (<1% at centers with >300 cases), minor for 1.7%. Risk of complications increased with number of leads removed (P<0.005) and with less experienced physicians (P<0.005); risk of major complications was higher for women (P<0.01). Given physician experience, appropriate precautions, and appropriate patient selection, contemporary lead removal techniques allow success with low complication rates.

Adolescent↗
PubMed1998

Transport of long-chain native fatty acids across human erythrocyte ghost membranes.

Evidence from a number of laboratories suggests that membrane proteins may meditate the transport of physiologic fatty acids (FA) across cell membranes. However, actual transport of unbound free fatty acids (unbound FFA) from the aqueous phase on one side of a cell membrane to the aqueous phase on the other side has not been measured previously. In this study, we have used the fluorescent probe of unbound FFA, ADIFAB, to monitor the time course of FA movement from the outer to the inner aqueous compartments, and from the lipid membrane to the outer aqueous compartment of red cell ghosts. These two measurements, together with measurements of the lipid/aqueous partition coefficients, allowed the determination of the rate constants for binding (kon), flip-flop (kff), and dissociation (koff) for the transport of long-chain natural FA across red cell ghosts. Measurements done using palmitate, oleate, and linoleate at temperatures between 20 and 37 degreesC revealed that the overall transport times ranged from about 0.5 to more than 10 s, depending upon FA type and temperature. Analysis of these time courses yielded kff values between 0.3 and 3.0 s-1, and these values were consistent with those obtained using ghosts containing pyranine to detect intracellular acidification by the translocating FA. The measured koff values ranged from about 0.3 to 5 s-1, while the rate of binding, for the ghost concentrations used in this study (>50 microM phospholipid), exceed both kff and koff. Thus, long-chain FA transport across red cell ghost membranes is rate-limited by a combination of flip-flop and dissociation rates. Binding of FA to ghost membranes was well described by simple, nonsaturable, aqueous/membrane partition, and that partition appears to be governed by the aqueous solubility of the FA. Transport rates did not reveal any evidence of saturation and were not affected by a variety of protein-specific reagents. These FA binding and transport characteristics are similar to those observed previously for lipid vesicles, although the rate constants are generally about 2-3 fold larger for ghosts as compared to the lipid vesicles. We suggest, therefore, that FA transport across red cell ghosts is reasonably well described by transport across the lipid phase of the membrane.

Arylsulfonates↗
PubMed1998

Transmigration of CD34+ cells across specialized and nonspecialized endothelium requires prior activation by growth factors and is mediated by PECAM-1 (CD31).

The transmigration of hematopoietic progenitor cells (HPCs) across vascular endothelium is a critical step in the homing of transplanted stem cells, but the molecular basis for this is unknown. We used mobilized peripheral blood CD34(+) selected cells and cultured bone marrow microvascular (BMECs) and human umbilical vein endothelial cells (HUVECs) to investigate the adhesion and transendothelial migration of HPCs. Colony-forming cells (CFCs) in freshly isolated CD34(+) cells showed high levels of adhesion to both forms of endothelium (28% +/- 4% and 38% +/- 6% of granulocyte-macrophage colony-forming cells [GM-CFCs] adhering to HUVECs and BMECs, respectively), but were unable to migrate to any significant extent across either (1.0% +/- 0.3% and 1.1% +/- 0.6% of GM-CFCs migrating across HUVECs and BMECs, respectively). Greater than 95% of peripheral blood CD34(+) cells are in G0/G1 of the cell cycle, but after 48 to 72 hours of stimulation with growth factors (interleukin-3 [IL-3] 12 ng/mL, stem cell factor 10 ng/mL, and IL-6 10 ng/mL), 28% +/- 5% of cells were in S+G2/M. Growth factor stimulation had no effect on the adhesion of mobilized CFCs but resulted in enhanced migration of these cells (9.8% +/- 1.6% and 12. 6% +/- 3.1% of GM-CFCs migrating across HUVECs and BMECs, respectively; P < .01, n = 6). Assessment of cell proliferation by the 3H-thymidine suicide method showed that, whereas 11.7% +/- 3.3% of proliferating CFCs transmigrated across endothelium, only 1.3% +/- 0.3% of nonproliferating CFCs did so (P < .05, n = 5). Transmigration of growth factor-activated CFCs was inhibited by anti-CD18 monoclonal antibody (MoAb; 50% +/- 18% inhibition) and by anti-platelet endothelial cell adhesion molecule-1 (PECAM-1) MoAb (70.8% +/- 7.1% inhibition; P < .05, n = 3). IL-1 stimulation of HUVECs had no significant effect on CD34(+) cell transmigration, but caused marked enhancement of neutrophil migration. Stem cell homing may depend, in part, on the ability of local cytokines to upregulate the transmigratory ability of these cells. The transmigration of HPCs shares at least some molecular pathways with that of mature cells (CD18 and PECAM-1), but is differently affected by endothelial activation.

Antigens, CD34↗
PubMed1998

Pharmacokinetics of interstitial delivery of carmustine, 4-hydroperoxycyclophosphamide, and paclitaxel from a biodegradable polymer implant in the monkey brain.

Polymeric interstitial chemotherapy increases survival of humans with recurrent gliomas and animals with transplanted tumors in the brain, but the relationship between rates of drug release from polymer implants and drug concentration in brain tissue is unknown. This work presents a pharmacokinetic framework for application of this new modality of chemotherapy delivery in primates. Either [3H]carmustine, 4-hydroperoxycyclophosphamide (4-HC), or paclitaxel was encapsulated in a polyanhydride pellet (28-41 microCi/animal, 40 mg/animal), which was implanted intracranially in cynomolgus monkeys (Macaca fascicularis); (n = 17) for up to 30 days. Drug concentrations in the brain, blood, and cerebrospinal fluid were measured by quantitative autoradiography, TLC, and scintillation counting. High drug concentrations (0.5-3.5 mM for carmustine, 0.3-0.4 mM for 4-HC, and 0.2-1.0 mM for paclitaxel) were measured within the first 3 mm from the polymer implant; significant (0.4 microM for carmustine, 3 microM for 4-HC, and 0.6 microM for paclitaxel) concentrations were measured up to approximately 5 cm from the implant as long as 30 days after implantation. Pharmacokinetic analysis indicated that tissue exposure to carmustine area under concentration-time curve achieved by polymeric delivery was 4-1200 times higher than that produced by i.v. administration of a higher dose.

Animals↗