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Biomedical subjects

H Schott

Publications and source records attributed to H Schott.

At least 55 records · Page 3Linked to original sources
PubMed1994

New lipophilic alkyl/acyl dinucleoside phosphates as derivatives of 3'-azido-3'-deoxythymidine: inhibition of HIV-1 replication in vitro and antiviral activity against Rauscher leukemia virus infected mice with delayed treatment regimens.

The antiretroviral activity of two new lipophilic derivatives of azidothymidine (AZT), N4-hexadecyl-2'-deoxyribocytidylyl-(3',5')-3'-azido-2',3'-deoxythy midine (N4-hexadecyldC-AZT) and N4-palmitoyl-2'-deoxyribocytidylyl-(3',5')-3'-azido-2',3'-deoxythy midine (N4-palmitoyldC-AZT) was evaluated in comparison to AZT. In vitro the drugs were tested in human immunodeficiency virus 1 (HIV-1) infected CD4+ HeLa and H9 cells. The in vivo antiviral effect of these derivatives was analysed in Rauscher leukemia virus (RLV) infected mice. The derivatives were incorporated into small liposomes. In vitro both derivatives inhibited virus proliferation in both HIV-1 infected cell lines in a similar dose-responsive manner as AZT. In a plaque reduction assay, using HeLa cells, the IC50 values were 0.035 microM for AZT, 0.5 microM for N4-hexadecyldC-AZT and 4.5 microM for N4-palmitoyldC-AZT, whereas p24 antigen analysis on H9 cells gave IC50 values of 0.005 microM, 0.05 microM and 0.05 microM, respectively. RLV infected mice were treated with intermittent schedules i.p. or i.v. on days 1, 6, 11, and days 16 or 0, 3, 7, and 11 after infection. Regimens with further delayed drug application were on days 3, 7, and 11 and 7 and 11 only. While i.p. treatment with total doses of 380-1140 mg/kg free AZT resulted in 10-30% inhibition of RLV induced splenomegaly, the derivatives gave inhibitions of 37-94%. Late onset of treatment with the derivatives was significantly more effective as compared to free AZT. Intravenous treatment with N4-hexadecyldC-AZT was effective, but with AZT was inactive. The discrepancy in antiviral activity of the AZT derivatives found between the in vitro and in vivo test systems emphasizes the importance of investigating the activity of drug derivatives in vivo.

Animals↗
PubMed1993

Neoadjuvant chemotherapy with carboplatin/5-fluorouracil in head and neck cancer.

In a prospective, randomized, multicenter study, neoadjuvant chemotherapy (CT) with carboplatin and 5-fluorouracil (5-FU) followed by locoregional treatment (LRT) was compared with locoregional treatment alone in the treatment of patients with head and neck cancer. This study, which includes 324 patients, was conducted from January 1988 to July 1991. The aim of this study was to evaluate the impact of the carboplatin/5-FU regimen both on the incidence of mutilating surgery and on the survival rate. Chemotherapy consisted of three cycles of carboplatin 400 mg/m2 day 1 and 5-FU 1 g/m2 days 1-5, repeated every 3 weeks. Patients with a complete tumor response then received radiotherapy alone, instead of the treatment planned initially. Three hundred patients were analyzed: 79 had tumors of the oral cavity, 106 oropharyngeal tumors, and 115 pharyngolaryngeal tumors. One hundred fifty patients underwent CT+LRT; 150 patients had LRT alone. Grade 3 and 4 toxicity rates were minimal in the CT+LRT group; toxicity was mainly hematologic (24% neutropenia, 19% thrombocytopenia). There were 3 toxic deaths (2%), 2 due to septicemia and 1 due to cardiac toxicity. One hundred forty-three patients were evaluable for efficacy. The tumor objective response rate was 63% and complete response rate was 31% (35% for oropharyngeal, 34% for pharyngolaryngeal tumors, 22.5% for oral cavity tumors), which led to a 29% decrease in the rate of mutilating surgery. Conservative treatment was performed in 57% of patients in the CT+LRT group vs. 24% in the LRT group (p = 0.001). There was no significant difference between survival curves in the CT+LRT and LRT groups. At 4 years, overall survival rates were 56 and 46%; disease-free survival rates were 33 and 30% in the CT+LRT and the LRT groups, respectively. The survival rates were not significantly different in the two groups. The locoregional recurrence rates were 35% in the CT+LRT arm and 25% in the LRT arm (p = 0.04), with median follow-up of 25 months. The rates of secondary localization and distant metastasis were not significantly different in the two groups.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Not Available].

Around 1800 the relationship between doctors and patients was determined by two opposing therapeutic principles, both of which were able to look back on a long tradition. On the one hand, the Enlightenment period lent prominence to the principle of correction, as can be traced paradigmatically in the field of orthopaedics. In this case medical treatment was closely linked to the conception of education. This approach emerged around 1800, particularly in the form of Brownianismus - in the field of psychiatry among others. At the same time the therapeutic principle of sympathy, which has its roots in magic healing, gained fresh impetus in the "electric age" of the Enlightenment, particularly through mesmerism (animal magnetism). Here it is a question of the hidden interdependence in nature, which gained considerable importance especially in the field of psychology on the early nineteenth century (in the context of the so-called Romantic Medicine). It is this area of tension, the combination of external correction and internal sympathy, which makes the period between Enlightenment and Romantic such a fascinating subject in the history of medicine.

History, 18th Century↗
PubMed1993

[The therapeutics of Paracelsus with reference to natural philosophy, alchemy and psychology].

The controversial reception of Paracelsus is still going on. The crucial question is whether he is a man of the Middle Ages or of modern times. It is not possible to give a simple answer. We have to study the writings of Paracelsus within the scientific and cultural context of the Renaissance. This period is characterized by a new concept of natural philosophy. The theory of signature tries to read or translate certain constellations within the natural environment as a secret code. The idea of a sympathetic correspondence between natural bodies or substances implies the possibility of magical healing. A wellknown example is the preparation of the 'weapon salve'. There are two realities of spiritual powers at the same time: demons from the outside of the human body and powers of the mind from its inside which influence the body functions. The natural philosophy of the Renaissance tries to 'naturalize' the demons as a complement of matter. Paracelsus reflects the ideas of his time. The human being has got two bodies: a visible one which belongs to earth and an invisible one which belongs to heaven. The 'philosopher' as a pharmacist and a doctor has to detect the invisible body corresponding with the celestial world (stars, planets) by analysing the manifest astrological signs. The alchemical preparation of remedies has to purify the specific healing substances ('arcana') from the crude material. The pharmacist and doctor just imitates artificially the quasi alchemical metabolic process of nature itself continuing and finishing it. Paracelsus' concept of imagination ('imaginatio') implies a psychosomatic model how far spiritual powers can influence the body functions. Paracelsus stresses radically the importance of suggestions as a source of illness. The synchronical concepts are confusing today. Knowledge and superstition, scientific rationality and irrational speculations come together and can hardly be separated. Nevertheless, at the end of the 20th century we may have more mental relations to this scenario than we are able to realize it at the moment.

Alchemy↗
PubMed1992

Labelling of liposomes with intercalating perylene fluorescent dyes.

The high fluorescent potential and the exceptional photostability of lipophilic derivatives of perylene-3,4:9,10-bis(dicarboximides) are utilized for the fluorescence-labelling of liposomes. The preparation of the liposomes is effected by supersonic starting from a lipid mixture consisting of the matrix lipids soy lecithin, cholesterol, alpha-tocopherol and the perylene dyes. From a multitude of perylene derivatives investigated only those are optimally incorporated into the bilayer membrane of unilamellar liposomes which are substituted at both nitrogen atoms by one or two linear hydrocarbon groups. In order to attain an optimal fluorescent quantum yield, about 200 to 300 dye molecules can be incorporated per liposome. The liposomes thus obtained have a diameter of about 70 to 80 nm, are homogeneous and may be stored for more than seven months. Neither the fluorescent properties nor the stability of these liposomes are influenced by the additional incorporation of various ara C-derivatives and lipophilic anchor groups which subsequently enable the coupling of antibodies to the liposomes. As the water-insoluble perylene dyes are incorporated into the bilayer membrane, the aqueous inner volume of the liposomes remains available for a further utilization.

Cholesterol↗
PubMed1992

Treatment of L1210 murine leukemia with liposome-incorporated N4-hexadecyl-1-beta-D-arabinofuranosyl cytosine.

N4-alkyl-1-beta-D-arabinofuranosyl cytosines as lipophilic derivatives of the widely used anti-tumor drug 1-beta-D-arabinofuranosylcytosine (ara-C) were synthesized and incorporated into unilamellar liposomes. The resulting preparations yielded stable unilamellar liposomes with diameters ranging between 40 and 70 nm. The liposomal derivatives exhibited an increased anti-tumor effect against the murine L1210 lymphoid leukemia at optimal molar concentrations which were 16 times lower than those previously reported for free ara-C. The N4-alkyl-ara-C derivatives with alkyl chains containing 14-16 C-atoms were highly effective against L1210 leukemia whereas shorter chains showed no cytostatic effects. The increased resistance to hydrolysis of the N4-alkyl-ara-C derivatives and the improved anti-tumor effect of the liposomal N4-hexadecyl-ara-C preparation compared to other known N4-acyl-ara-C prodrugs, together with the possibility of preparing large volumes of stable and sterile liposomes, hold out the prospect of more effective chemotherapy for leukemias.

Animals↗
PubMed1992

Kinetics of swelling of polymers and their gels.

The swelling limit or equilibrium swelling of semicrystalline or cross-linked polymers and of their gels upon immersion in liquids has been investigated extensively. Few studies, however, have dealt with the kinetics of swelling. Theoretical considerations, based on diffusion-controlled swelling, show that first-order kinetics do not apply, even though deviations during the initial and even middle stages of the swelling process may be relatively small. Extensive studies of swelling rate and equilibrium swelling of supported and unsupported gelatin films have been published. Diffusion was always fast. After it was completed, the rate of swelling was controlled by stress relaxation in the amorphous portion of the polymer network. The rate equations for this process, which also apply to regenerated cellulose, are shown to represent second-order kinetics with respect to the remaining swelling capacity. The following interpretation for the applicability of second-order kinetics to the swelling of semicrystalline polymers, such as gelatin and cellulose, is given. The rate of swelling is assumed to be directly proportional to the percent swelling capacity still available at a given time and to the total internal specific boundary area enclosing those sites capable of swelling that have not yet become hydrated and swollen at that time. The latter, in turn, is also directly proportional to the percent unrealized swelling capacity.

Chemistry, Pharmaceutical↗
PubMed1992

[Not Available].

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History, Ancient↗
PubMed1990

Comparative studies of the preparation of immunoliposomes with the use of two bifunctional coupling agents and investigation of in vitro immunoliposome-target cell binding by cytofluorometry and electron microscopy.

The two coupling agents SPDP (N-succinimidyl-3-(2-pyridyldithio)propionate) and SATA (N-succinimidyl-S-acetylthioacetate) were compared in their efficiency and feasibility to couple monoclonal antibodies (Abs) via thioether linkage to liposomes functionalized by various lipophilic maleimide compounds like N-(3-maleimidopropionyl)-N2-palmitoyl-L-lysine methyl ester (MP-PL), N-(3-maleimidopropionyl)phosphatidylethanolamide (MP-PE), N6-(6-maleimidocaproyl)-N2-palmitoyl-L-lysine methyl ester (EMC-PL), and N-(6-maleimidocaproyl)phosphatidylethanolamine (EMC-PE). The composition of the liposomes was soy phosphatidylcholine (SPC), cholesterol, maleimide compounds and alpha-tocopherol (1:0.2:0.02:0.01, mol parts), plus N4-oleylcytosine arabinoside (NOAC) as cytostatic prodrug (0.2 mol parts) and a new, lipophilic and highly fluorescent dye N,N'-bis(1-hexylhfetyl)-3,4:9,10-perylenebis(dicarboximid ) (BHPD, 0.006 mol parts). From the maleimide derivatives MP-PL was the most effective in terms of preservation of the coupling activity in dependence of liposome storage. The coupling of the monoclonal A B8-24.3 (mouse IgG2b, MHC class I, anti H-2kb) and IB16-6 (rat IgG2a, anti B16 mouse melanoma) to the drug carrying liposomes was more effective and easier to accomplish with SATA as compared to SPDP. Coupling rates of 60-65% were obtained with SATA at molar ratios of 12 SATA:1 Ab:40 maleimide spacer groups on the surface of one liposome. The highest coupling rates with SPDP were obtained at the ratio of 24 SPDP:1 Ab:40 liposomal maleimide groups, with an Ab binding efficiency of only 20-25%. The optimal in vitro binding conditions to specific target cells (EL4 for B8-24.3-liposomes and B16-F10 for IB16-6-liposomes) were determined by cytofluorometric measurement of the liposomal BHPD fluorescence with SATA linked Abs. Optimal immunoliposome binding to specific epitopes on the target cells was achieved with 1-2 Ab molecules coupled to one liposome, with immunoliposome concentrations of 20-130 nM and with a small incubation volume of 0.3-0.4 ml. The specificity of the binding of B8-24.3-liposomes to EL4 target cells was visualized by scanning electron microscopy. Antibody mediated endocytic uptake of immunoliposomes could be demonstrated by transmission electron microscopy.

Animals↗
PubMed1990

Cerebral blood flow and rheologic alterations by hyperosmolar therapy in patients with brain oedema.

Cerebral blood flow was assessed as initial slope index by 133-Xenon inhalation in 36 patients with brain tumours subjected to osmotic dehydration. The following solutions were employed: I. 20% mannitol, II. 40% sorbitol, III. 10% glycerol. Parameters affecting blood rheologic properties as Hct, plasma viscosity, red blood cell aggregation and fluidity were simultaneously studied. CBF which was reduced in the oedematous hemisphere with brain tumour increased during infusion and thereafter by mannitol or sorbitol, respectively. The blood flow response to glycerol was more delayed, less intense, but maintained longer. Hct and plasma viscosity were significantly reduced by all osmotic agents, while red blood cell fluidity fell and aggregation rose under mannitol. It is concluded that sorbitol (40%) is superior for emergency treatment with high ICP, whereas glycerol seems to be preferable to improve cerebral blood flow in oedematous brain.

Cerebrovascular Circulation↗
PubMed1988

[Preparation of homologs of oligoribouridylic acid by selective partial hydrolysis of RNA].

The preparation of oligouridylic acids was achieved by the stepwise partial hydrolysis of RNA using enzymatical and chemical methods of degradation followed by chromatographic purification steps. After RNA is submitted first to RNase T1 and after that to RNase U2 it is cleaved into oligopyrimidine nucleotides carrying purine nucleotides only at their 3'-terminal. By chemical deamination the pyrimidine sequences are converted to oligouridine sequences. After enzymatical dephosphorylation of the oligouridylic acids their 3'-terminal purine nucleosides are eliminated by a periodate-lysine treatment. The phosphate groups remaining at the 3'-terminal of the resulting oligouridylic acids are enzymatically removed. As a result of the partial hydrolysis the mean recoveries of the particular homologues are U2-U7 93% and U8 86% adding up to about 0.5% of the amount of RNA used as starting material.

Base Sequence↗
PubMed1988

Chromatography of functionalized liposomes and their components.

The antitumour drug 1-beta-D-arabinofuranosylcytosine (ara C) was acylated by means of oleic acid anhydride, resulting in the prodrug N4-oleoyl-ara C. Together with a lipophilic biotin derivative, this lipophilic prodrug was incorporated into the bilayer membrane of unilamellar liposomes prepared by means of the detergent dialysis method. On addition of these biotinylated prodrug-liposomes to an excess of avidin, biotin residues were complexed with avidin. The unreacted avidin was removed by chromatography on the Ultrogel AcA-22 column. The prodrug-liposome-avidin complex was coupled to biotinylated monoclonal antibodies through the free binding sites of the immobilized avidin. Unreacted antibodies were removed by chromatography on an Ultrogel AcA-22 column. In vitro, the liposome-antibody complexes selectively bound to cells which were recognized by the monoclonal antibodies linked to the liposomes. For this reason, a promising strategy towards a specific chemotherapy of cancer is expected.

Avidin↗
PubMed1988

Palmitoyl derivatives of L-cysteine, cysteamine, L-cystine, cystamine and their incorporation into the bilayers of unilamellar liposomes.

The amino groups of the amino acids L-cysteine and L-cystine as well as their biogene amines cysteamine and cystamine were derivatized with palmitoyl residues. The obtained lipophilic R-SH and R-S-S-R components were incorporated into the bilayers of unilamellar liposomes. The resulting liposomes carrying about 2000 functional groups each remained stable and homogeneous during 60 days after incorporation of N-palmitoyl cysteamine and N,N'-dipalmitoyl cystamine. The incorporation of the lipophilic amino acid derivatives, however, destabilized the resulting liposomes. Via the thiol residues of the functionalized liposomes activated molecules can be linked to the liposomal surface by disulfide bonds.

Amino Acids↗
PubMed1988

Isoelectric points of some sulfonamides: determination by microelectrophoresis and by calculations involving acid-base strength.

The isoelectric points of four very slightly soluble sulfonamides were measured by microelectrophoresis of dilute suspensions as a function of pH. Ionic strength and pH were adjusted with KCl, KOH, and HCl only. The isoelectric points were also calculated from published values of acid and basic ionization constants which had been determined by potentiometric titration, and from changes in ultraviolet absorption spectra and in solubility as a function of pH. Including one sulfonamide whose isoelectric point as measured by microelectrophoresis was published, rather good agreement between the two methods was observed for all but one compound. All values were between 3.5 and 4.6, indicating that the sulfonamides function as weak acids rather than as amphoteric compounds at physiological pH.

Chemical Phenomena↗
PubMed1988

[Not Available].

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Germany↗