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Biomedical subjects

E Schacht

Publications and source records attributed to E Schacht.

At least 19 recordsLinked to original sources
PubMed2007

Superiority of a combined treatment of Alendronate and Alfacalcidol compared to the combination of Alendronate and plain vitamin D or Alfacalcidol alone in established postmenopausal or male osteoporosis (AAC-Trial).

A combined therapy with the strongly antiresorptive Alendronate and the pleiotropically acting D-hormone analogue Alfacalcidol may have additive effects on bone quality, falls and fracture risk in established osteoporosis. The aim of this study (Alfacalcidol Alendronate Combined-AAC) was to compare the efficacy and safety of a combined parallel therapy with Alendronate and Alfacalcidol to the treatment with either Alendronate in combination with plain vitamin D or Alfacalcidol alone in patients with established postmenopausal or male osteoporosis. Ninety patients were included as matched triplets to receive randomly either 1 microg Alfacalcidol daily + 500 mg calcium (group A, n = 30) or 70 mg Alendronate weekly + 1,000 mg calcium + 1,000 IU vitamin D daily (group B, n = 30) or 1 microg Alfacalcidol daily + 70 mg Alendronate weekly + 500 mg calcium daily (group C, n = 30). Patients were recruited in one centre and were followed up for 24 months. Analysis was intention-to-treat and the primary outcome was lumbar spine and total hip bone mineral density (measured observer blind). BMD was measured at the lumbar spine and at the proximal femur with dual energy X-ray absorptiometry (LUNAR Prodigy, GE, USA) at the beginning and after 12 and 24 months. During the 2-year-study we observed descriptively significant increases at the lumbar spine of 3.0% in group A compared to baseline, of 5.4% in group B and of 9.6% in group C, respectively. The superiority of the Alendronate + Alfacalcidol treatment group over Alfacalcidol alone and over Alendronate + vitamin D was of more than large rele-vance (both tests: MW > 0.71; CI-LB > 0.64; P < 0.001). We also observed median increases of the BMD at the total hip of 1.5% in group A, of 2.4% in group B and of 3.8% in group C, respectively. The superiority of group C over group A and over group B again was relevant and statistically significant in a descriptive sense. After 2 years there was a tendency towards higher rates of vertebral and non-vertebral fractures in group A and B as compared to C. Taking both fracture types together we observed 9, 10 and 2 "osteoporotic fractures" in groups A, B and C, respectively. The comparison of group C with pooled groups A and B and with each single group gave a relevantly lower fracture rate for the combination of Alendronate and Alfacalcidol. Furthermore a lower rate of falls was observed for the combination Alendronate plus Alfacalcidol versus Alendronate + vitamin D, but not versus Alfacalcidol alone. We found 80% of the patients in the Alendronate + Alfacalcidol group free from back pain at month 24, compared to 30% in the Alendronate + vitamin D and 43% in the Alfacalcidol monotherapy group. The superiority is relevant (both tests: MW > 0.64; CI-LB > 0.56; P < 0.003). Pain decrease also occurred more rapidly in the Alendronate + Alfacalcidol group than in the other groups. In general side effects in all groups were mild, and only four cases of moderate hypercalcuria in group A and one in group C were reported, but no case of hypercalcemia was documented. In conclusion, the combination therapy with Alendronate and Alfacalcidol exhibited superiority in terms of BMD, overall fractures, rate of falls and back pain over either Alendronate in combination with plain vitamin D or Alfacalcidol alone. The overall safety profiles of the three treatment regimens were found to be not different in this study.

Aged↗
PubMed2005

Vitamin D analogs versus native vitamin D in preventing bone loss and osteoporosis-related fractures: a comparative meta-analysis.

It has been suggested that early postmenopausal women and patients treated with steroids should receive preventive therapy (calcium, vitamin D, vitamin D analogs, estrogens, or bisphosphonates) to preserve their bone mineral density (BMD) and to avoid fragility fractures. We designed the present study to compare the effects of native vitamin D to its hydroxylated analogs alfacalcidol 1-alpha(OH)D and calcitriol 1,25(OH)(2)D. All randomized, controlled, double-blinded trials comparing oral native vitamin D and its analogs, alfacalcidol or calcitriol, to placebo or head-to-head trials in primary or corticosteroids-induced osteoporosis were included in the meta-analysis. Sources included the Cochrane Controlled Trials Register, EMBASE, MEDLINE, and a hand search of abstracts and references lists. The study period January 1985 to January 2003. Data were abstracted by two investigators, and methodological quality was assessed in a similar manner. Heterogeneity was extensively investigated. Results were expressed as effect-size (ES) for bone loss and as rate difference (RD) for fracture while allocated to active treatment or control. Publication bias was investigated. Fourteen studies of native vitamin D, nine of alfacalcidol, and ten of calcitriol fit the inclusion criteria. The two vitamin D analogs appeared to exert a higher preventive effect on bone loss and fracture rates in patients not exposed to glucocorticoids. With respect to BMD, vitamin D analogs versus placebo studies had an ES of 0.36 (P < 0.0001), whereas native vitamin D versus placebo had an ES of 0.17 (P = 0.0005), the interclass difference being highly significant (ANOVA-1, P < 0.05). When restricted to the lumbar spine, this intertreatment difference remained significant: ES = 0.43 (P = 0.0002) for vitamin D analogs and ES = 0.21 (P = 0.001) for native vitamin D (analysis of variance [ANOVA-1], P = 0.047). There were no significant differences regarding their efficacies on other measurement sites (ANOVA-1, P = 0.36). When comparing the adjusted global relative risks for fracture when allocated to vitamin D analogs or native vitamin D, alfacalcidol and calcitriol provided a more marked preventive efficacy against fractures: RD = 10% (95% Confidence interval [CI-2] to 17) compared to RD = 2% (95% CI, 1 to 2), respectively. The analysis of the spinal and nonspinal showed that fracture rates differed between the two classes, thereby confirming the benefits of vitamin D analogs, with significant 13.4% (95% CI 7.7 to 19.8) and. 6% (95% CI 1 to 12) lower fracture rates for vitamin D analogs, respectively. In patients receiving corticosteroid therapy, both treatments provided similar global ESs for BMD: ES = 0.38 for vitamin D analogs and ES = 0.41 for native vitamin D (ANOVA-1, P = 0.88). When restriced to spinal BMD, D analogs provided significant effects, whereas native vitamin D did not: ES = 0.43 (P < 0.0001) and ES = 0.33 (P = 0.21), respectively. The intertreatment difference was nonsignificant (ANOVA-1, P = 0.52). Neither D analogs for native vitamin D significantly prevented fractures in this subcategory of patients: RD = 2.6 (95%CI, -9.5 to 4.3) and RD = 6.4 (95%CI, -2.3 to 10), respectively. In head-to-head studies comparing D analogs and native vitamin D in patients receiving corticosteroids, significant effects favoring D analogs were found for femoral neck BMD: ES = 0.31 at P = 0.02 and spinal fractures: RD = 15% (95%CI, 6.5 to 25). Publication bias was not significant. Our analysis demonstrates a superiority of the D analogs atfacalcidol and calcitriol in preventing bone loss and spinal fractures in primary osteoporosis, including postmenopausal women. In corticosteroid-induced osteoporosis, the efficacy of D analogs differed depending on the comparative approach: indirect comparisons led to nonsignificant differences, whereas direct comparison did provide significant differences. In this setting, D analogs seem to prevent spinal fractures to a greater extent than do native vitamin D, but this assumption should be confirmed on a comprehensive basis in multiarm studies including an inactive comparator.

Adrenal Cortex Hormones↗
PubMed2005

In vivo efficiency of targeted norfloxacin against persistent, isoniazid-insensitive, Mycobacterium bovis BCG present in the physiologically hypoxic mouse liver.

Persistence of Mycobacterium tuberculosis is a hypoxia-inducible state in which the bacteria are phenotypically insensitive to currently available antituberculous drugs. In humans, persistent M. tuberculosis is found in granulomatous lesions, either inside macrophages or in necrotic tissue, where the partial oxygen pressure (pO(2)) is very low. Persistent bacteria can remain silent for decades before overt tuberculosis develops. Due to insensitivity to classical drugs, M. tuberculosis persistence prevents rapid and definitive clearance of bacteria. Consequently, therapeutic molecules are required that are both active against persistent bacilli and able to reach their intramacrophagic location. In contrast to its native form, norfloxacin is active in vivo against Mycobacterium bovis BCG present in the lungs when temporarily linked to a macromolecular carrier targeted to macrophages. To study the efficiency of this macromolecular prodrug targeted to persistent mycobacteria confined inside macrophages, we established a short-term in vivo model based on the physiological pO(2) differences between lungs, spleen and liver. Whereas lungs and spleen are well oxygenated, the liver has a low pO(2) due to its portal irrigation. Therefore, studying mycobacteria in the liver yields information about in vivo persistent bacilli exposed to low pO(2). To our knowledge, no similar short-term in vivo model has been published to date. Using this model, we demonstrated the insensitivity to isoniazid of M. bovis BCG present in hypoxic sites, and showed that norfloxacin given as a mannosylated macrophage-targeted prodrug was able to kill these isoniazid-insensitive mycobacteria. This demonstrates that intracellular persistent mycobacteria are amenable to antibiotic treatment.

Animals↗
PubMed2004

Polymeric prodrugs.

In 1975 Prof. H. Ringsdorf proposed a model for rational design of polymeric prodrugs [J. Polym. Sci. Symp. 51 (1975) 135]. The model has been the most important basis for research in the field, since it was the first model that took into account both the chemical and biological aspects needed for the design of polymeric prodrugs. This paper deals with the most important properties that were discovered by designing polymeric prodrugs: prolongation of action of the drug, controlled release of the drug, passive tumor accumulation by the EPR-effect and alteration of body distribution and cell uptake. Over the years, other objectives have been formulated and other properties of polymer-drug conjugates were discovered. One recent example, the immunoprotective ability of polymeric prodrugs, is described in more detail in this paper.

Adjuvants, Immunologic↗
PubMed2004

Endometrial safety with a low-dose intrauterine levonorgestrel-releasing system after 3 years of estrogen substitution therapy.

OBJECTIVE: To evaluate the pharmacodynamic effects of a novel intrauterine drug delivery system, FibroPlant-levonorgestrel (LNG), on the endometrium in 24 postmenopausal women using estrogen substitution therapy (EST) to suppress climacteric symptoms. DESIGN: A 3-year non-comparative prospective clinical trial. SUBJECTS: The treatment with the FibroPlant-LNG intrauterine system (IUS), releasing 14 microg of LNG per day, was part of a regimen for estrogen substitution therapy in symptomatic postmenopausal women to prevent endometrial proliferation and bleeding. The majority of women received percutaneous 17 beta estradiol, 1.5 mg daily, or an equivalent dose by patch or orally, on a continuous basis. OUTCOME MEASURES: Menstrual pattern, endometrial histology and ultrasonographic evidence of endometrial suppression, after 3 years of use. RESULTS: The endometrial histology specimen showed profound endometrial suppression with glandular atrophy and stroma decidualization in all women. On transvaginal ultrasound, this corresponds with a thin endometrium (<5 mm) and clinically with a "bleed-free" menstrual pattern or amenorrhoea. CONCLUSION: The results of this 3-year study in 24 postmenopausal women using EST suggest that the FibroPlant-LNG IUS is effective in causing strong suppression of the endometrium during the entire period of EST. Target delivery in the uterine cavity could be the preferred route of administering a progestin to oppose estrogen stimulation of the endometrium.

Aged↗
PubMed2004

[Biomaterials].

Biomaterials are essential components in the development of artificial organs. Synthetic polymers are widely used for a number of biomedical applications: a) as medical supplies, b) devices to support or replace malfunctioning body parts or c) systems with a local therapeutic function. The design of biomaterials has developped over the past three decades from devices with a mechanical function, over systems with a dedicated function (degradable, drug releasing, surface modified) to devices which are tailor made to interact in a smart way with the biological environment. At present polymers are attractive materials to construct scaffolds for tissue regeneration and regenerative medicine. The material design is adapted to the requirements for cell ingrowth, cell migration, angiogenesis etc. This is mainly controlled by the surface topography and chemistry that play a key role in the interfacial material-cell communication. This remarkable development is the direct result of a multi-disciplinary approach, combining material science with engineering, cell biology, molecular biology, medicine and regulatory guidelines.

Animals↗
PubMed2003

Superiority of alfacalcidol over plain vitamin D in the treatment of glucocorticoid-induced osteoporosis.

Supplementation therapy with plain vitamin D plus calcium is in general regarded as effective prevention or first-step treatment of glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to compare the therapeutic efficacy of the D-hormone analog alfacalcidol with plain vitamin D in patients with established GIOP with or without vertebral fractures. Patients on long-term glucocorticoid (GC) therapy were included as matched pairs to receive randomly either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n=103) or 1000 IU vitamin D3 plus 500 mg calcium (group B, n=101). The two groups were well matched in terms of mean age, sex ratio, mean height and weight, daily dosage, and duration of GC therapy, and the percentages of the three underlying diseases included chronic obstructive pulmonary disease, rheumatoid arthritis, and polymyalgia rheumatica. The baseline mean bone mineral density (BMD) values at the lumbar spine for the two groups were -3.26 (alfacalcidol) and -3.25 (vitamin D(3)) and, at the femoral neck, -2.81 and -2.84, respectively (T scores). Rates of prevalent vertebral and nonvertebral fractures did not differ between groups. During the 3-year study, we observed a median percentage increase of BMD at the lumbar spine of 2.4% in group A and a loss of 0.8% in group B ( P<0.0001). There also was a larger median increase at the femoral neck in group A (1.2%) than in group B (0.8%) ( P<0.006). The 3-year rates of patients with at least one new vertebral fracture were 9.7% among those assigned to the alfacalcidol group and 24.8% in the vitamin D group (risk reduction 0.61, 95% CI 0.24-0.81, P=0.005). The 3-year rates of patients with at least one new nonvertebral fracture were 15% in the alfacalcidol group and 25% in the vitamin D group (risk reduction 0.41, 95% CI 0.06-0.68, P=0.081). The 3-year rates of patients with at least one new fracture of any kind were 19.4% among those treated with alfacalcidol and 40.65% with vitamin D (risk reduction 0.52, 95% CI 0.25-0.71, P=0.001). In accordance with the observed fracture rates, the alfacalcidol group showed a substantially larger decrease in back pain than the plain vitamin D group ( P<0.0001). Generally, side effects in both groups were mild, and only three patients in the alfacalcidol group and two in the vitamin D group had moderate hypercalcemia. We conclude that alfacalcidol plus calcium is highly superior to plain vitamin D3 plus calcium in the treatment of established GIOP.

Adjuvants, Immunologic↗
PubMed2003

Performance and acceptability of intrauterine release of levonorgestrel with a miniature delivery system for hormonal substitution therapy, contraception and treatment in peri and postmenopausal women.

OBJECTIVE: To evaluate the performance and acceptability of a novel intrauterine drug delivery system, FibroPlant-levonorgestrel (LNG), delivering approximately 14 microg per day. SUBJECT AND DESIGNS: A 1-year prospective clinical trial in 141 peri and postmenopausal women, including women with heavy or postmenopausal bleeding and women needing contraception. The majority received percutaneous 17beta-estradiol (Oestrogel), 1.5 mg daily. Clinical results and ultrasonographic effects were evaluated. RESULTS: Eighty-three insertions were done in perimenopausal women and 58 in postmenopausal women followed-up for 8-38 months. Fifty-two perimenopausal (64%) and virtually 100% of the postmenopausal women developed amenorrhoea, with occasional slight spotting. Eleven women with heavy bleeding, five of them with single or multiple intramural and subserosal fibroids of 3-6 cm or more, were all successfully treated, except one. There were no pregnancies. CONCLUSION: This study of 1432 women-months of use suggests that the frameless FibroPlant-LNG IUS is safe, well tolerated and effective in suppressing the endometrium during EST. The fact that the IUS also acts as a contraceptive, and significantly reduces menstrual bleeding, as demonstrated in earlier studies, is of added importance.

Adult↗
PubMed2003

Use of block copolymers of poly(ortho esters) and poly (ethylene glycol) micellar carriers as potential tumour targeting systems.

Amphiphilic AB and ABA block copolymers have been prepared from poly (ortho esters) and poly (ethylene glycol). Such block copolymers readily form micellar dispersions in water, or buffers. The CMC is in the range of 3 x 10(-4)-5 x 10(-4) g/l which is a value low enough to assure retention of micelle integrity upon intravenous injection. The size, as determined by dynamic light scattering was in the 40-70 nm range. The micelles can be stored in lyophilized form for at lest 8 months and easily reconstituted to the original properties. The micelles are stable in PBS at pH 7.4 and 37 degrees C for 3 days and in a citrate buffer at pH 5.5 and 37 degrees C for 2 h. Stability in the presence of bovine serum albumin depends on the structure of the block copolymer and especially the length of the POE block.

Drug Carriers↗
PubMed2002

The effect on menstrual blood loss in women with uterine fibroids of a novel "frameless" intrauterine levonorgestrel-releasing drug delivery system: a pilot study.

OBJECTIVE: To evaluate the effect on menstrual blood loss, in women with uterine fibroids, of a novel "frameless" intrauterine drug delivery system (IUS), FibroPlant-levonorgestrel (LNG), releasing 14 microg of LNG per day. STUDY DESIGN: An open label, non-comparative ongoing pilot study. Fourteen insertions were performed in premenopausal women between 39 and 48 years of age for the treatment of menorrhagia. The effect on menstrual blood loss was evaluated using a simple visual assessment technique. Women were followed-up for at least 12 months (range 12-30 months). RESULTS: At the time of study analysis the total number of women-months was 283. All women, except one reported greatly reduced bleeding. In two women, the treatment failed although both reported reduced bleeding. One failure (patient no. 4) was due to the presence of a large endometrial polyp. This patient underwent hysterectomy. The other women (patient no. 1) had submucosal fibroids. She refused hysterectomy and is continuing treatment. In the other 12 patients, reduction of bleeding was appreciable after one month of treatment and tended to decrease further over the next months to stabilize afterwards. The mean bleeding score before treatment was 465 (185-960) and dropped to a mean score of 100 (range 5-300) after a minimum of 12 months of treatment which is highly statistically significant (P<0.001). In eight women, the bleeding reduced to very low scores. An effect on the size of the uterine fibroids could not be demonstrated. Significant spotting was rare after the first 3 months following insertion. Neither complications (e.g. infection, expulsion or perforation) nor pregnancies occurred. The FibroPlant-LNG IUS was well tolerated by all women involved in the study and no systemic hormonal side effects were reported. CONCLUSION: This study suggests that FibroPlant-LNG IUS is effective to significantly reduce the amount of menstrual blood loss in women with menorrhagia in the presence of intramural and subserosal fibroids and can avoid surgery. The strong endometrial suppression is the principal mechanism explaining the effect on menstrual blood loss of the IUS. The two failures probably explain that a successful treatment in women with endometrial abnormalities (e.g. polyps, submucous fibroids) is unlikely with the IUS. The low daily release rate of LNG from the FibroPlant-LNG IUS results in a low incidence of hormonal side effects. The simple design characteristics and revolutionary anchoring system account for minimizing the occurrence of complaints of pain and expulsion. The flexible fibrous delivery system adapts to cavities of every size even when severely distorted.

Adult↗
PubMed2002

Contraception and treatment in the perimenopause with a novel "frameless" intrauterine levonorgestrel-releasing drug delivery system: an extended pilot study.

The objective of the study was to evaluate the contraceptive performance, acceptability, side effects, and adverse events of a novel "frameless" intrauterine drug delivery system (IUS), FibroPlant-levonorgestrel (LNG) releasing 14 microg of LNG/day, in perimenopausal women. An ancillary objective was to evaluate the effect of the new IUS on menstrual blood loss in women with or without fibroids. The study, consisting of 109 women, suggests that FibroPlant-LNG IUS is an effective contraceptive. No pregnancies occurred with the FibroPlant-LNG IUS. The total use-related discontinuation rate at 1 year is low (1.9) and results in a high rate of continuation of use (98.1). In addition, the FibroPlant-LNG IUS demonstrated a high level of effectiveness in reducing bleeding in women with excessive menstrual flow even when medium or large fibroids were present. However, an effect on the size of the fibroids could not be demonstrated. Patient satisfaction with the method is high, which is a prerequisite for continuance of the method, and may be linked with the advantageous design characteristics of the FibroPlant-LNG IUS, the virtual absence of hormonal side effects, and the low incidence of irregular bleeding and spotting even during the first 3 months after insertion of the FibroPlant IUS. Counseling remains important though to explain to women about the possible occurrence of changes in their menstrual pattern that may sometimes be annoying but harmless. It is concluded that many women over age 40 years could substantially benefit from the advantages of this intrauterine drug delivery technology which provides contraception and treatment of a possible associated condition such as menorrhagia. The treatment also creates the opportunity to pass through the transitional perimenopausal period smoothly and to benefit fully from the advantages hormone replacement therapy offers in terms of treatment of short-term symptoms and long-term prevention by gradually replacing the waning estrogens.

Adult↗
PubMed2001

Ab initio and experimental study on thermally degradable polycarbonates: the effect of substituents on the reaction rates.

Thermal elimination reactions on polycarbonates are investigated from both theoretical and experimental points of view, to obtain insight into the microscopic aspects that influence the reaction mechanism and rates. In particular, attention is focused on the influence of the type of substituents in the polymer chain on the reaction rates. Ab initio density functional theory calculations are performed on a series of model compound systems for the polycarbonates under study, in particular carbonates differing by the groups attached at the alpha and beta carbon atoms. Reactants, products, and transition states are optimized at the B3LYP/6-311g level of theory. The structures of the activated complex give insight into the mechanistic details of this type of E(i) elimination reactions. The C(alpha)-O bond dissociates before the C(beta)-H bond, developing some carbocation character in the transition state on the C(alpha) atom. The kinematics of the thermal decomposition reactions have been studied by means of transition state theory by construction of the microscopic partition functions. It turns out that the rates of the E(i) elimination reactions are increased by the presence of those substituents on the C(alpha) and C(beta) carbon atoms which are stabilizing the carbocation character in the transition state. In a second part, degradation temperatures have been experimentally measured for some polycarbonates through thermogravimetric analysis. It is investigated whether the relative rates of the model compound carbonate systems are representative of the behavior of the thermal degradation temperatures in polycarbonates. The study as presented here proves that ab initio calculations on small model systems, which are representative for the active area of the degradation process in polycarbonates, can provide insight into the principal ingredients that govern the reaction rates.

Journal Article↗
PubMed2001

Preparation and characterisation of rose Bengal-loaded surface-modified albumin nanoparticles.

Surface-modified albumin nanoparticles were prepared from two poly(ethylene glycol)-human serum albumin conjugates: poly(thioetheramido acid)-poly(ethylene glycol) copolymer-grafted HSA (HSA-PTAAC-PEG) and methoxy poly(ethylene glycol)-grafted HSA (HSA-mPEG). Rose bengal (RB) was used as a model drug for encapsulation into the nanoparticles either during the particle production or by adsorption post particle preparation. The drug incorporation and release was affected by the different production methods and the different polymer compositions. When RB was loaded in HSA and HSA/HSA-PTAAC-PEG nanoparticles, up to 5% (w/w) drug content was achieved. The drug loading in HSA-mPEG nanoparticles was much lower and the results from the microcalorimetry study indicated that the low loading efficiency was due to less drug-protein binding sites available in the HSA-mPEG molecule as compared to the HSA molecule. The release of RB from the albumin nanoparticles was very slow in PBS and dramatically accelerated in the presence of trypsin. Compared with unmodified nanoparticles, the slower release of RB from the surface-modified HSA nanoparticles in the presence of the enzyme suggested that the existence of a steric hydrophilic barrier on the surface of the nanoparticles made digestion of the nanoparticles more difficult.

Administration, Oral↗
PubMed2001

Generation of class-selective monoclonal antibodies against the penicillin group.

To develop a penicillin-specific ELISA, different attempts were made to obtain monoclonal antibodies specific for the common structure of penicillins. Ampicillin was coupled to different carrier proteins (bovine serum albumin, chicken ovalbumin, and thyroglobulin) to render it immunogenic. Different coupling methods were compared: two methods using a cross-linker (glutaraldehyde or a succinimide ester), one carbodiimide-mediated coupling method, and one method without any cross-linker or mediator molecule (physiological binding). Mice were immunized with the conjugates intraperitoneally or in the footpad. A screening ELISA was developed to detect anti-ampicillin antibodies in sera. Specificity and affinity of the antibodies were demonstrated by inhibiting their binding with a 10 mM solution of ampicillin. No difference could be observed using electrofusion or PEG-mediated fusion. For the production of the monoclonals, an intravenous final boost gave antibodies with better specificity and affinity than an intraperitoneal final booster injection. At least one anti-ampicillin monoclonal antibody (19C9) cross-reacts with penicillin G, oxacillin, dicloxacillin, and carbenicillin, and not with sulfanilamide, chloramphenicol, neomycin, and streptomycin, and is therefore considered interesting for developing a penicillin-specific ELISA.

Animals↗
PubMed2001

Incorporation of salicylic acid derivatives to hydrophilic copolymer systems with biomedical applications.

Hydrogels based on polymeric derivatives of salicylic acid have been prepared for biomedical applications by free radical copolymerization of 2-hydroxy-4-methacrylamidobenzoic acid, 4HMA, and 2-hydroxy-5-methacrylamidobenzoic acid, 5HMA, with 2- hydroxyethylmethacrylate, HEMA, in a wide range of compositions. The reactivity ratios of 4HMA and 5HMA with HEMA in radical copolymerization processes have been determined from their 1H NMR spectra by applying linearization methods and non-linear least square treatments. Tgs of the corresponding copolymers were analyzed by DSC. The swelling behavior in water of the prepared copolymers was studied in comparison to poly-(HEMA), poly-(4HMA) and poly-(5HMA) hydration degrees, being in all cases superior to 35%. The hydrolytical behavior of the synthesized copolymers was studied at three different pHs (2, 7.4 and 10) determining the release percentage of the salicylic acid derivatives, 4-amino salicylic acid, 4ASA, and 5-amino salicylic acid, 5ASA, analyzed by high performance liquid chromatography (HPLC). The release analysis was followed during 230 days and a pH dependence was observed obtaining the highest release percentages at pH=10, whereas at physiological pH (7.4) the release percentages were in range from 2 to 5% at that time for all copolymer systems. The hydrolytical stability is enough for long-term applications like bone cements, ionomers, etc.

Journal Article↗
PubMed2001

Treatment of menorrhagia with a novel 'frameless' intrauterine levonorgestrel-releasing drug delivery system: a pilot study.

OBJECTIVE: To evaluate the effect on menstrual blood loss of a novel 'frameless' intrauterine drug delivery system, the FibroPlant levonorgestrel intrauterine system (IUS), releasing 14 microg of levonorgestrel/day. An ancillary objective was to evaluate the contraceptive performance. STUDY DESIGN: This was an open-label, non-comparative ongoing pilot study. Thirty-two insertions were performed in fertile women aged between 31 and 51 years for the treatment of menorrhagia, as well as for contraceptive purposes. Fifteen women who developed excessive bleeding were fitted with the FibroPlant levonorgestrel IUS immediately following the removal of a copper-bearing intrauterine device (IUD), the GyneFix IUD. To discriminate between menorrhagia and normal menstrual blood loss, women were evaluated using a simple visual assessment technique. The trial covered a period from a minimum of 1 month up to 23 months. RESULTS: At the time of study analysis, the total number of woman-months was 361. Fourteen of the women had had the FibroPlant levonorgestrel IUS in place for more than 1 year, and 29 women for 6 months or more. All women reported greatly reduced bleeding. However, no cases of amenorrhea resulting from endometrial suppression were encountered. The reduction of bleeding was substantial after 1 month of treatment and decreased further over the next months to remain stable thereafter. The mean bleeding score before treatment was 338 (range 185-740) in the group who had had no prior use of an IUD and 368 (range 185-890) in the group with prior IUD use. The mean bleeding score dropped to a mean score of 70 (range 5-210) in the 'no prior IUD use' group and to a mean score of 52 (range 3-150) in the 'prior IUD use' group, after 1-23 months of follow-up. This result is highly statistically significant (p < 0.001). There were no statistical differences in bleeding scores before and during treatment between the two groups of women, with or without prior use of the copper IUD. Significant spotting was rare after the first 3 months following insertion. No complications (e.g. infection, expulsion or perforation) or pregnancies occurred. The FibroPlant levonorgestrel IUS was well tolerated by all women involved in the study and no systemic hormonal side-effects were reported. CONCLUSION: The FibroPlant levonorgestrel IUS is effective in significantly reducing the amount of menstrual blood loss in women with menorrhagia. Strong endometrial suppression is the principal mechanism explaining both the effect on menstrual blood loss and the contraceptive performance of the IUS. There were no differences in bleeding scores before and during treatment between the two groups of women with or without prior use of the copper IUD, suggesting that the development of heavy bleeding was not related to the use ofthe IUD. The therapeutic effect of this contraceptive method is highly desirable, particularly in women with heavy bleeding or anemia in developing countries, as other treatment modalities are less effective, more costly, more invasive or inaccessible. The low daily release rate of levonorgestrel from the FibroPlant levonorgestrel IUS results in a low incidence of hormonal side-effects and reduces the likelihood of amenorrhea. The simple design characteristics and revolutionary anchoring system minimize the occurrence of complaints of pain and the incidence of expulsion.

Adult↗