Biomedical subjects

U Zimmermann

Publications and source records attributed to U Zimmermann.

At least 55 records · Page 3Linked to original sources

PubMed2001

Phloretin-induced changes of lipophilic ion transport across the plasma membrane of mammalian cells.

The adsorption of the hydrophobic anion [W(CO)(5)CN](-) to human lymphoid Jurkat cells gave rise to an additional anti-field peak in the rotational spectra of single cells, indicating that the cell membrane displayed a strong dielectric dispersion in the kilohertz to megahertz frequency range. The surface concentration of the adsorbed anion and its translocation rate constant between the two membrane boundaries could be evaluated from the rotation spectra of cells by applying the previously proposed mobile charge model. Similar single-cell electrorotation experiments were performed to examine the effect of phloretin, a dipolar molecule known to influence the dipole potential of membranes, on the transport of [W(CO)(5)CN](-) across the plasma membrane of mammalian cells. The adsorption of [W(CO)(5)CN](-) was significantly reduced by phloretin, which is in reasonable agreement with the known phloretin-induced effects on artificial and biological membranes. The IC(50) for the effect of phloretin on the transport parameters of the lipophilic ion was approximately 10 microM. The results of this study are consistent with the assumption that the binding of phloretin reduces the intrinsic dipole potential of the plasma membrane. The experimental approach developed here allows the quantification of intrinsic dipole potential changes within the plasma membrane of living cells.

Adsorption↗

PubMed2001

Tumour-related enzyme alterations in the clear cell type of human renal cell carcinoma identified by two-dimensional gel electrophoresis.

To identify tumour-related enzyme alterations we have used 2D-gels to analyse the proteome from dissected malignant and benign kidney areas from patients with clear-cell-type renal carcinoma. The expression of 12 proteins was diminished in tumour. Four proteins were characterized by mass spectrometry and were identified as enoyl-CoA hydratase, alpha-glycerol-3-phosphate dehydrogenase, aldehyde dehydrogenase 1 and aminoacylase-I.

Aldehyde Dehydrogenase↗

PubMed2001

[The physiopathology of weight regulation during treatment with psychotropic drugs].

Weight changes during pharmacological treatment are a well-known phenomenon and they have been an object of research since the 1950's. Weight gain occurs during treatment with drugs of different chemical structures and is an important problem when patients are treated with antidepressants, antipsychotics, or mood stabilizers. The clinical relevance of drug-induced weight changes is due to increased rates of morbidity and reduced treatment compliance. Regarding the underlying causes, the important role of neurotransmitter systems and in particular the blockade of serotonin and histamine receptors has been discussed since decades. Only recently, however, research has been started on the effects of psychotropic agents on major neuroendocrine systems involved in appetite and weight regulation. These studies suggest that the fat-cell derived hormone leptin might play an important role. Leptin signals to the brain the size of the adipose tissue and is probably the most important peripheral signal for the long-term regulation of weight. In addition to the neuroendocrine systems, weight gain induced by psychotropic agents might also involve immune modulators, in particular the proinflammatory cytokine tumor-necrosis-factor-alpha (TNF-alpha) and soluble TNF-receptors. Some psychotropic agents influence the TNF system very rapidly, already prior to any obvious increases in weight. Hence, changes in the TNF-alpha system might be of predictive value for drug-induced weight gain. Strategies to minimize or to counteract weight gain induced by psychotropic agents include psychotherapeutic and pharmacological approaches. Although numerous psychotherapeutic approaches are available, they are only of limited usefulness in severely ill psychiatric patients. Fortunately, a number of promising pharmacological approaches to reduce weight have been introduced into clinical practice during the last years; however, so far there is no knowledge on pharmacodynamic and -kinetic interactions with psychotropic drugs, and there is no clinical data on the usefulness and safety of such drug combinations.

Animals↗

PubMed2001

A novel class of amitogenic alginate microcapsules for long-term immunoisolated transplantation.

In the light of results of clinical trials with immunoisolated human parathyroid tissue Ba2+-alginate capsules were developed that meet the requirements for long-term immunoisolated transplantation of (allogeneic and xenogeneic) cells and tissue fragments. Biocompatibility of the capsules was achieved by subjecting high-M alginate extracted from freshly collected brown algae to a simple purification protocol that removes quantitatively mitogenic and cytotoxic impurities without degradation of the alginate polymers. The final ultra-high-viscosity, clinical-grade (UHV/CG) product did not evoke any (significant) foreign body reaction in BB rats or in baboons. Similarly, the very sensitive pERK assay did not reveal any mitogenic impurities. Encapsulated cells also exhibited excellent secretory properties under in vitro conditions. Despite biocompatible material, pericapsular fibrosis is also induced by imperfect capsule surfaces that can favor cell attachment and migration under the release of material traces. This material can interact with free end monomers of the alginate polymers under formation of mitogenic advanced glycation products. Smooth surfaces, and thus topographical biocompatibility of the capsules (visualized by atomic force microscopy), can be generated by appropriate crosslinking of the UHV/CG-alginate with Ba2+ and simultaneous suppression of capsule swelling by incorporation of proteins and/or perfluorocarbons (i.e., medically approved compounds with high oxygen capacity). Perfluorocarbon-loaded alginate capsules allow long-term non-invasive monitoring of the location and the oxygen supply of the transplants by using 19F-MRI. Transplantation studies in rats demonstrated that these capsules were functional over a period of more than two years.

Alginates↗

PubMed2001

The combined dexamethasone-suppression/CRH-stimulation test in alcoholics during and after acute withdrawal.

BACKGROUND: Chronic alcoholism is often accompanied by disturbances of the hypothalamic-pituitary-adrenal (HPA) system. Patients with alcoholism frequently show nonsuppression in the dexamethasone (Dex) suppression test and also a blunted increase of adrenocorticotropin (ACTH) after injection of corticotropin-releasing hormone (hCRH). However, the underlying mechanisms have not been fully elucidated. The combined Dex/CRH test (pretreatment with 1.5 mg dexamethasone at 2300 hr, injection of 100 microg hCRH at 1500 hr the next day) has been established as a more sensitive tool to investigate HPA system regulation in depressed patients. METHODS: We studied the effect of the combined Dex/CRH test in 19 alcoholic inpatients (9 male, 10 female) during and after withdrawal along with 19 healthy controls. RESULTS: Compared to normal controls, patients showed a severely dysregulated HPA system during withdrawal, with significantly elevated cortisol and ACTH response to hCRH after pretreatment with dexamethasone. After completed withdrawal, cortisol levels after injection of hCRH were almost normalized while ACTH values were partially lower in patients, compared to controls. CONCLUSIONS: We conclude that the HPA system is severely disturbed during alcohol withdrawal, possibly reflecting an exaggerated release of hypothalamic corticotropin and vasopressin.

Adrenocorticotropic Hormone↗

PubMed2000

Conversion from cyclosporine A to tacrolimus after kidney transplantation due to hyperlipidemia.

As more than 90% of renal grafts retain their function 1 year after renal transplantation, side effects of immunosuppressive therapy gain more and more importance. In a randomised prospective study, we investigated the effects of conversion from cyclosporine A to tacrolimus due to hyperlipidemia in recipients of renal allografts. Fifty-seven patients with stable graft function treated with cyclosporine were randomly assigned to conversion to tacrolimus or continuation of their current therapy and followed for 1 year. Twenty-seven patients were switched and 30 patients remained on cyclosporine A. Cholesterol levels decreased significantly in the tacrolimus group as compared to controls in the intent to treat analysis. When only those patients were evaluated who received cyclosporine or tacrolimus during the whole study, statistical significance was even more pronounced. Triglyceride levels decreased in the tacrolimus group, whereas they increased in controls. Creatinine levels remained stable and no acute rejection was observed. A switch to tacrolimus is a safe alternative in cases of hyperlipidemia after renal transplantation.

Adult↗

PubMed2000

Biocompatible alginate from freshly collected Laminaria pallida for implantation.

A simple procedure is described for the extraction and purification of alginate from the inner stipes of the kelp Laminaria pallida. Alginate yield was about 10-15% of the dry mass, with a 70:30 mannuronic/guluronic acid ratio. Analysis of the purified alginate revealed a low polyphenol content while proteins were below detection level. The purified alginate was highly viscous, with 10-15 mPa s and 281 mPa s for a 0.1% and 0.5% solution, respectively, indicating a very high molecular mass (larger than 250 kDa). Bead formation occurred in the presence of divalent cations, but also in the presence of artificial serum (FCSIII) without added divalent cations. The biocompatibility of the alginate was tested with the in vitro mice lymphocyte test as well as by implantation of Ba2+ cross-linked beads beneath the kidney capsule of BB/OK rats. There was no evidence for significant mitogenic activity or fibrotic reaction. Biocompatibility of the alginate was also demonstrated by the encapsulation of human chondrocytes into Ca2+ cross-linked alginate beads. Immobilized chondrocytes grew and remained functional (i.e. they produced collagen).

Alginates↗

PubMed2000

Parathyroid xenotransplantation without immunosuppression in experimental hypoparathyroidism: long-term in vivo function following microencapsulation with a clinically suitable alginate.

Permanent hypoparathyroidism is one of the most difficult of all endocrine disorders to treat medically. Because this deficiency syndrome rarely is a life-threatening condition, systemic immunosuppression for recipients of transgenic transplants is not justified. An alternative would be protecting the tissue to be transplanted from the immunologic response (immunoisolation) by coating it with a semipermeable membrane- microencapsulation. Unfortunately, prior to the first clinical use, further analysis of the coating substance (alginate) demonstrated that it has potential cancerogenic properties. Using a purified amitogenic alginate suitable for clinical use, we accomplished allotransplantation in a long-term animal model and reported the first clinical cases without postoperative immunosuppression recently. In view of the potential clinical use, we investigated the ability of the microencapsulation technology with the novel amitogenic alginate in experimental hypoparathyroidism (80 parathyroidectomized rats) to enable transgenic transplantation across the highest immunologic barrier (xenotransplantation: human to rat) to ensure intact transplant function without immunosuppression. In a controlled, long-term animal study, the effect of microencapsulation on xenotransplanted human parathyroid tissue was evaluated over a period of 30 weeks (microencapsulated and naked hyperplastic parathyroid tissue, respectively). Functionally, human parathyroid tissue was able to replace that of rats. More than 6 months after xenotransplantation 32 of 40 animals that had received microencapsulated transplants were normocalcemic. In contrast, serum calcium concentrations dropped to postparathyroidectomy levels within 3 weeks in the animals that had received naked tissue only. Correspondingly, normocalcemic animals showed vital parathyroid tissue inside the microcapsules, which were surrounded by a small rim of fibroblasts. When combining microencapsulation with an improved tissue culture method, xenotransplantation of human parathyroid tissue and maintenance of its physiologic function is reproducibly achieved over the highest transplantation barrier. Using the amitogenic alginate may be a crucial step toward the first clinical use of this technique for parathyroid xenotransplantation without immunosuppression.

Alginates↗

PubMed2000

Effect of fluorine substitution on the interaction of lipophilic ions with the plasma membrane of mammalian cells.

The effects of the anionic tungsten carbonyl complex [W(CO)(5)SC(6)H(5)](-) and its fluorinated analog [W(CO)(5)SC(6)F(5)](-) on the electrical properties of the plasma membrane of mouse myeloma cells were studied by the single-cell electrorotation technique. At micromolar concentrations, both compounds gave rise to an additional antifield peak in the rotational spectra of cells, indicating that the plasma membrane displayed a strong dielectric dispersion. This means that both tungsten derivatives act as lipophilic ions that are able to introduce large amounts of mobile charges into the plasma membrane. The analysis of the rotational spectra allowed the evaluation not only of the passive electric properties of the plasma membrane and cytoplasm, but also of the ion transport parameters, such as the surface concentration, partition coefficient, and translocation rate constant of the lipophilic anions dissolved in the plasma membrane. Comparison of the membrane transport parameters for the two anions showed that the fluorine-substituted analog was more lipophilic, but its translocation across the plasma membrane was slower by at least one order of magnitude than that of the parent hydrogenated anion.

Animals↗

PubMed2000

Molecular characterization of anion exchangers in the cochlea.

Anion exchange proteins (AE) in the inner ear have been the focus of attention for some time. They have been suggested to play a role as anion exchangers for the regulation of endolymphatic pH or as anion exchangers and anchor proteins for the maintenance of the shape and turgor of outer hair cells, and they also have been discussed as a candidate protein for motile hair cell responses that follow high-frequency stimulation. The existence of anion exchangers in hair cells and the specific isoforms which are expressed in hair cells and the organ of Corti is controversial. Using a polyclonal antibody to AE1 (AB 1992, Chemicon), we immunoprecipitated a 100 kDa AE polypeptide in isolated outer hair cells which, due to its glycosylation, is comprised of AE2 than AE1 isoforms. We confirmed AE2 expression in outer hair cells with the help of subtype-specific monoclonal and polyclonal antibodies to AE, AE subtype-specific primers and AE subtype-specific cDNA and found glycosylated truncated as well as full-length AE2 isoforms. No AE1 or AE3 subtypes were noted in outer hair cells. In contrast, AE2 and AE3 but not AE1 subtypes were seen in supporting cells of the organ of Corti. Their expression preceded the development of cochlear function, coincident with the establishment of the endocochlear potential and the differentiation of supporting cells. While most developmental processes in the inner ear usually begin in the basal cochlear turn, the AE2 expression in outer hair cells (but not that of AE2 and AE3 in supporting cells) progressed from the apical to the basal cochlear turn, reminiscent of the maturation of frequency-dependency. Irrespective of their presumed individual role as either anion exchanger, anchor protein or motility protein, the differential expression and developmental profile of these proteins suggest a most important role of anion exchange proteins in the development of normal hearing. These findings may also provide novel insights into AE function in general.

Animals↗

PubMed2000

In vivo laser-induced fluorescence detection of pyrene in nematodes and determination of pyrene binding constants for humic substances by fluorescence quenching and bioconcentration experiments.

The bioconcentration of pyrene by bacterivorous thread worms (nematodes) of the species Caenorhabditis elegans was studied with laser-induced fluorescence (LIF) spectroscopy, fluorescence imaging and a radiotracer method. The vibronic band intensities of the LIF spectra indicated that the microenvironment of pyrene in the nematodes was similar to a low-polarity solvent, and thus provided direct evidence that pyrene was accumulated in lipid-rich areas inside the nematodes. The concentration of pyrene in the nematodes was estimated from the monomer/excimer fluorescence intensity ratio. Results from this method were in fair agreement with results using 14C labeled pyrene for measuring pyrene bioconcentration. Preliminary results indicated that LIF measurements of pyrene may be possible even in single nematodes. Fluorescence microscopic observations revealed that pyrene was not adsorbed on the outside of the organisms, but was strongly concentrated in restricted areas inside the worms. In the second part of the study, the effects of six different humic substances (HS) on the bioconcentration of pyrene were investigated and sorption coefficients (KDOC) calculated from reductions in bioconcentration (KDOC(biol)) were compared with sorption coefficients measured with a fluorescence quenching technique (KDOC(flu)). The results of these two different experimental methods agreed well (with KDOC(biol) being slightly lower than KDOC(flu), indicating that the fraction of pyrene that was determined as freely dissolved by the fluorescence quenching method was comparable to the bioavailable fraction.

Adsorption↗

PubMed2000

Xylem conduits of a resurrection plant contain a unique lipid lining and refill following a distinct pattern after desiccation.

The axial and radial refilling with water of cut dry branches (up to 80 cm tall) of the resurrection plant Myrothamnus flabellifolia was studied in both acro- and basipetal directions by using 1H-NMR imaging. NMR measurements showed that the conducting elements were not filled simultaneously. Axial water ascent occurred initially only in a cluster of a very few conducting elements. Refilling of the other conducting elements and of the living cells was mainly achieved by radial extraction of water from these initial conducting elements. With time, xylem elements in a few further regions were apparently refilled axially. Radial water spread through the tissue occurred almost linearly with time, but much faster in the acropetal than in the basipetal direction. Application of hydrostatic pressure (up to 16 kPa) produced similar temporal and spatial radial refilling patterns, except that more conducting elements were refilled axially during the first phase of water rise. The addition of raffinose to the water considerably reduced axial and radial spreading rates. The polarity of water climbing was supported by measurements of the water rise in dry branches using the 'light refraction'(and, sometimes, the 'leaf recurving') method. Basipetal refilling of the xylem conduit exhibited biphasic kinetics; the final rise height did not exceed 20-30 cm. Three-cm-long branch pieces also showed a directionality of water climbing, ruling out the possibility that changes in the conducting area from the base to the apex of the branches were responsible for this effect. The polarity of water ascent was independent of gravity and also did not change when the ambient temperature was raised to c. 40 degrees C. At external pressures of 50-100 kPa the polarity disappeared, with basipetal and acropetal refill times of the xylem conduit of tall branches becoming comparable. Refilling of branches dried horizontally (with a clinostat) or inverted (in the direction of gravity) showed a pronounced reduction of the acropetal water rise to or below basipetal water climbing level (which was unaffected by this treatment). Unlike water, benzene and acetone climbing showed no polarity. In the case of benzene, the rise kinetics (including the final heights) were comparable with those measured acropetally for water, whereas with acetone the rise height was less. Transmission electron microscopy of dry branches demonstrated that the inner surfaces of the conducting tracheids and vessels were lined with a continuous osmiophilic (lipid) layer, as postulated by the kinetic analysis and light microscopy studies. The thickness of the layer varied between 20 and 80 nm. The parenchymal and intervessel pits as well as numerous tracheid corners contained opaque inclusions, presumably also consisting of lipids. Electron microscopy of rehydrated plants showed that the lipid layer was either thinned or had disintegrated and that numerous vesicle-like structures and lipid bodies were formed (together with various intermediate structural elements). These, many other data and the physical-chemical literature imply that several (radial) driving forces (such as capillary condensation, Marangoni forces, capillary, osmotic and turgor pressure forces) operate when a few conducting elements become axially refilled with water. These forces apparently lead to an avalanche-like radial refilling of most of the conducting elements and living cells, and thus to the removal of the 'internal cuticle' and of the hydrophobic inclusions in the pits. The polarity of water movement presumably results from high resistances in the basipetal direction, which are created by local gradients in the thickness of the lipid film as a result of draining under gravity in response to drought. There are striking similarities in morphology and function between the xylem-lining lipid film and the lung surfactant film lining the pulmonary air spaces of mammals.

Acetone↗

PubMed2000

Water rise kinetics in refilling xylem after desiccation in a resurrection plant.

The acropetal water refilling kinetics of the dry xylem of branches (up to 80 cm tall) of the resurrection plant Myrothamnus flabellifolia were determined with high temporal resolution by observation of light refraction at the advancing water front and the associated recurving of the folded leaves. To study the effect of gravity on water rise, data were acquired for cut upright, horizontal and inverted branches. Water rise kinetics were also determined with hydrostatic and osmotic pressure as well as at elevated temperatures (up to 100 degrees C) under laboratory conditions and compared with those obtained with intact (rooted) and cut branches under field conditions. Experiments in which water climbed under its capillary pressure alone, showed that the axial flow occurred only in a very few conducting elements at a much higher rate than in many of the other ones. The onset of transpiration of the unfolded and green leaves did not affect the rise kinetics in the 'prominent' conducting elements. Application of pressure apparently increased the number of elements making a major contribution to axial xylem flow. Analysis of these data in terms of capillary-pressure-driven water ascent in leaky capillaries demonstrated that root pressure, not capillary pressure, is the dominant force for rehydration of rooted, dry plants. The main reasons for the failure of capillary forces in xylem refilling were the small, rate-limiting effective radii of the conducting elements for axial water ascent (c. 1 micrometer compared with radii of the vessels and tracheids of c. 18 micrometers and 3 micrometers, respectively) and the very poor wetting of the dry walls. The contact (wetting) angles were of the order of 80 degrees and decreased on root or externally applied hydrostatic pressure. This supported our previous assumption that the inner walls of the dry conducting elements are covered with a lipid layer that is removed or disintegrates upon wetting. Consistent with this, potassium chloride and, particularly, sugars exerted an osmotic pressure effect on axial water climbing (reflection coefficients > zero, but small). Although the osmotically active solutes apparently suppressed radial water spread through the tissue to the leaf cells, they reduced the axial water ascent rather than accelerating it as predicted by the theory of capillary-driven water rise in leaky capillaries. Killing cells by heat treatment and removal of the bark, phelloderm, cortex and phloem also resulted in a reduction of the axial rise rate and final height. These observations demonstrated that radial water movement driven by the developing osmotic and turgor pressure in the living cells was important for the removal of the lipid layer from the walls of those conducting elements that were primarily not involved in water rise. There is some evidence from field measurements of the axial temperature gradients along rooted branches that interfacial (Marangoni) streaming facilitated lipid removal (under formation of vesicle-like structures and lipid bodies) upon wetting. Grant numbers: 50WB 9643, Zi 99/9-1.

Biological Transport, Active↗

PubMed2000

[Thiamine treatment in psychiatry and neurology].

Every physician knows that alcohol dependence, alcohol withdrawal and Wernicke-Korsakow-syndrome require substitution with thiamine, in acute stages even parenterally. This would be trivial if there was not the widespread fear of anaphylactic, even lethal reactions to parenteral thiamine application. The present article reviews the literature published on thiamine since 1936, when the first synthetic, parenteral thiamine preparation became available, and, on this basis, tries to give practical advice and therapeutic regimens for the treatment of thiamine deficiency states. Controlled clinical studies on indications and differential thiamine therapy have not been published. From the data that are available, the following conclusions can be drawn: 1) Acute mortality of Wernicke-Korsakow-syndrome is about 20%. 2) Oral thiamine is safe. 3) The risk for an anaphylactic shock due to parenteral thiamine administration is below 1 to 100,000. 4) Not only alcohol but any condition with either increased metabolic need (pregnancy, consuming diseases) or deficient nutrition (including eating disorders) can lead to thiamine deficiency. Therefore, we suggest: 1) Oral thiamine substitution with at least 50 mg per day and supply of a sufficient and complete diet should be given to any person that might be at risk for thiamine deficiency. 2) Any patient suspicious for acute thiamine deficiency needs to be treated under inpatient conditions and there needs to receive 50 to 100 mg thiamine intravenously 3 to 4 times a day. 3) General practitioners, psychiatrists and neurologists should take care of the oral supplementation of thiamine, sufficient nutrition, and they are the physicians to diagnose early stages of thiamine deficiency.

Humans↗

PubMed2000

Thyroid hormone deficiency before the onset of hearing causes irreversible damage to peripheral and central auditory systems.

Both a genetic or acquired neonatal thyroid hormone (TH) deficiency may result in a profound mental disability that is often accompanied by deafness. The existence of various TH-sensitive periods during inner ear development and general success of delayed, corrective TH treatment was investigated by treating pregnant and lactating rats with the goitrogen methimazole (MMI). We observed that for the establishment of normal hearing ability, maternal TH, before fetal thyroid gland function on estrus days 17-18, is obviously not required. Within a crucial time between the onset of fetal thyroid gland function and the onset of hearing at postnatal day 12 (P12), any postponement in the rise of TH-plasma levels, as can be brought about by treating lactating mothers with MMI, leads to permanent hearing defects of the adult offspring. The severity of hearing defects that were measured in 3- to 9-mo-old offspring could be increased with each additional day of TH deficiency during this critical period. Unexpectedly, the active cochlear process, assayed by distortion product otoacoustic emissions (DPOAE) measurements, and speed of auditory brain stem responses, which both until now were not thought to be controlled by TH, proved to be TH-dependent processes that were damaged by a delay of TH supply within this critical time. In contrast, no significant differences in the gross morphology and innervation of the organ of Corti or myelin gene expression in the auditory system, detected as myelin basic protein (MBP) and proteolipid protein (PLP) mRNA using Northern blot approach, were observed when TH supply was delayed for few days. These classical TH-dependent processes, however, were damaged when TH supply was delayed for several weeks. These surprising results may suggest the existence of different TH-dependent processes in the auditory system: those that respond to corrective TH supply (e.g., innervation and morphogenesis of the organ of Corti) and those that do not, but require T3 activity during a very tight time window (e.g. , active cochlear process, central processes).

Animals↗

PubMed2000

Hydrogel-based non-autologous cell and tissue therapy.

Many diseases are closely tied to deficient or subnormal metabolic and secretory cell functions. Milder forms of these diseases can be managed by a variety of treatments. However, it is often extremely difficult or even impossible to imitate the moment-to-moment fine regulation and the complex roles of the hormone, factor or enzyme that is not sufficiently produced by the body. Immunoisolated transplantation is one of the most promising approaches to overcome the limitations of current treatments. Non-autologous (transformed) cell lines and allogeneic and xenogeneic cells/tissues that release the therapeutic substances are enclosed in immunoprotective microcapsules. The microcapsules avoid a lifetime of immunosuppressive therapy while excluding an immune response in the host. Research in this direction has shown the feasibility of microcapsules based on hydrogels (particularly of alginate) for transplantation of non-autologous cells and tissue fragments. Numerous technical accomplishments of the immunoisolation method have recently made possible the first successful long-term clinical applications. However, realizing the potential of immunoisolated therapy requires the use of several factors that have received limited attention in the past but are important for the formulation of hydrogel-based immunoisolation systems that are highly versatile, potentially economical and can gain medical approval.

Alginates↗

PubMed2000

Non-invasive evaluation of the location, the functional integrity and the oxygen supply of implants: 19F nuclear magnetic resonance imaging of perfluorocarbon-loaded Ba2+-alginate beads.

19F nuclear magnetic resonance imaging (MRI) can be used as a non-invasive tool to simultaneously determine the location, the integrity and the oxygen supply of Ba2+-alginate implants. This requires that the beads (implants) are pre-loaded with the perfluorocarbon compound F-44E. Implantation of solid 19F-labelled beads into the peritoneum, below the kidney capsule or into the muscle of Wistar WU rats demonstrated that these beads could be detected by 19F-MRI for up to 18 months after implantation. This indicated that F-44E is not considerably released from the beads during implantation. The signal to noise ratio of liquid-core beads was higher by a factor of 4 than the signal to noise ratio of solid beads, but liquid-core beads were more fragile and also too large for implantation under the kidney capsule and into the intramuscular tissue. Quantitative 2-dimensional 19F-T1 maps (resolution 0.5 x 0.5 mm) could be deduced from 19F-MRI measurements. These T1-maps correlated to the local pO2-values. The partial oxygen pressure estimated in F-44E-loaded Ba2+-alginate beads showed that the oxygen supply inside the beads was very poor when they were implanted below the kidney capsule or into the peritoneal cavity. These low pO2-values obtained for the renal subcapsular site and the peritoneum may explain the failure of previous immunoisolated islet transplantation studies using these locations.

Alginates↗

PubMed2000

[Disseminated mucormycosis in AIDS].

Mucormycosis is a rare often fatal opportunistic condition. It mainly occurs in immunocompromised subjects but rarely in AIDS patients. An eighteen-year-old HIV+ man from Zaire died rapidly from disseminated mucormycosis with pulmonary, cardiac, renal, hepatic, splenic and gastric involvement. Fungi were observed in all these organs with a particular vascular trophism. Rhizopus orizae was identified on cultures. Rapid microscopic diagnosis, in the localized stage, could improve the poor prognosis of this infection.

AIDS-Related Opportunistic Infections↗